Cancer Research and Treatment

Original Articles

High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment: Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim; Cancer Res Treat. 2020;52(1):98-108. Published online May 27, 2019; DOI: https://doi.org/10.4143/crt.2019.195

Purpose
The aim of this study was to develop a formalin-fixed paraffin-embedded (FFPE) tissue based multiplex immunochemistry (mIHC) method for high-throughput comprehensive tissue imaging and demonstrate its feasibility, validity, and usefulness.
Materials and Methods
The mIHC protocol was developed and tested on tissue microarray slides made from archived gastric cancer (GC) tissue samples. On a single FFPE slide, cyclic immunochemistry for multiple markers of immune cells and cytokeratin for tumor cells was performed; hematoxylin staining was used for demarcation of nuclei. Whole slides were digitally scanned after each cycle. For interpretation of mIHC results, we performed computer-assisted image analysis using publicly available software.
Results
Using mIHC, we were able to characterize the tumor microenvironment (TME) of GCs with accurate visualization of various immune cells harboring complex immunophenotypes. Spatial information regarding intratumoral and peritumoral TME could be demonstrated by digital segmentation of image guided by cytokeratin staining results. We further extended the application of mIHC by showing that subcellular localization of molecules can be achieved by image analysis of mIHC results.
Conclusion
We developed a robust method for high-throughput multiplex imaging of FFPE tissue slides. The feasibility and adaptability of mIHC suggest that it is an efficient method for in situ single-cell characterization and analysis.

Citations

Citations to this article as recorded by

Exploring Multiplex Immunohistochemistry (mIHC) Techniques and Histopathology Image Analysis: Current Practice and Potential for Clinical Incorporation
Aria Kaiyuan Sun, Song Fan, Siu Wai Choi
Cancer Medicine.2025;[Epub] CrossRef
The immunologic phenotype of thrombi is associated with future vascular events after cerebral infarction
Wookjin Yang, Soon Auck Hong, Jeong-Min Kim, Hae-Bong Jeong, Taek-Kyun Nam, Hyun Ho Choi, Suh Min Kim, Kwang-Yeol Park, Hye Ryoun Kim
Journal of NeuroInterventional Surgery.2024; 16(4): 352. CrossRef
The tumor immune microenvironment remodeling and response to HER2‐targeted therapy in HER2‐positive advanced gastric cancer
Lei Jiang, Xingwang Zhao, Yilin Li, Yajie Hu, Yu Sun, Shengde Liu, Zizhen Zhang, Yanyan Li, Xujiao Feng, Jiajia Yuan, Jian Li, Xiaotian Zhang, Yang Chen, Lin Shen
IUBMB Life.2024; 76(7): 420. CrossRef
HCR spectral imaging: 10-plex, quantitative, high-resolution RNA and protein imaging in highly autofluorescent samples
Samuel J. Schulte, Mark E. Fornace, John K. Hall, Grace J. Shin, Niles A. Pierce
Development.2024;[Epub] CrossRef
iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice
Jihye Kim, Jee Hyun Kim, Younghoon Kim, Jooyoung Lee, Hyun Jung Lee, Seong-Joon Koh, Jong Pil Im, Joo Sung Kim
Histochemistry and Cell Biology.2024; 162(5): 415. CrossRef
Immunohistochemistry for assessing toxicity and mechanism of action of anticancer drugs during preclinical trials. From theory to practice
M. A. Dodokhova, M. A. Akimenko, O. V. Voronova, M. S. Alkhusein-Kulyaginova, N. A. Kornienko, M. V. Gulyan, D. N. Gyulmamedov, M.-M. Kh. Alasheva, E. Sh. Kazimagomedova, D. B. Shpakovsky, E. R. Milaeva, I. M. Kotieva
Fundamental and Clinical Medicine.2024; 9(3): 74. CrossRef
Nontoxic Fluorescent Nanoprobes for Multiplexed Detection and 3D Imaging of Tumor Markers in Breast Cancer
Pavel Sokolov, Galina Nifontova, Pavel Samokhvalov, Alexander Karaulov, Alyona Sukhanova, Igor Nabiev
Pharmaceutics.2023; 15(3): 946. CrossRef
Automatic generation of pathological benchmark dataset from hyperspectral images of double stained tissues
Jiansheng Wang, Xintian Mao, Yan Wang, Xiang Tao, Junhao Chu, Qingli Li
Optics & Laser Technology.2023; 163: 109331. CrossRef
Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer
Dharambir Kashyap, Amanjit Bal, Santosh Irinike, Siddhant Khare, Shalmoli Bhattacharya, Ashim Das, Gurpreet Singh
Applied Immunohistochemistry & Molecular Morphology.2023; 31(8): 533. CrossRef
Exploring the Complex and Multifaceted Interplay between Melanoma Cells and the Tumor Microenvironment
Magdalena Kuras
International Journal of Molecular Sciences.2023; 24(18): 14403. CrossRef
New insights into the tumour immune microenvironment of nasopharyngeal carcinoma
Aisling Forder, Greg L. Stewart, Nikita Telkar, Wan L. Lam, Cathie Garnis
Current Research in Immunology.2022; 3: 222. CrossRef
Let us not forget about our past contributions to the field of prostatic neoplasms: To some extent what we value now was already there
Rodolfo Montironi, Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Gregor Mikuz
Pathology - Research and Practice.2021; 219: 153377. CrossRef
Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate -Induced Gastritis
Du-Min Go, Seung Hyun Lee, Su-Hyung Lee, Sang-Ho Woo, Kibyeong Kim, Kyeongdae Kim, Kyu Seong Park, Jong-Hwan Park, Sang-Jun Ha, Woo Ho Kim, Jae-Hoon Choi, Dae-Yong Kim
Cellular and Molecular Gastroenterology and Hepatology.2021; 12(2): 715. CrossRef
Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry
Yujun Park, An Na Seo, Jiwon Koh, Soo Kyoung Nam, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee
OncoImmunology.2021;[Epub] CrossRef
Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry
Hee Young Na, Yujun Park, Soo Kyung Nam, Jiwon Koh, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Kyu Sang Lee, Hye Seung Lee
Journal of Translational Medicine.2021;[Epub] CrossRef
Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers
Rui Wei, Si Liu, Shutian Zhang, Li Min, Shengtao Zhu
Analytical Cellular Pathology.2020; 2020: 1. CrossRef
Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy
Laura Bracci, Alessandra Fragale, Lucia Gabriele, Federica Moschella
Frontiers in Immunology.2020;[Epub] CrossRef

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Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study: Joon Mee Kim, Jin Hee Sohn, Mee-Yon Cho, Woo Ho Kim, Hee Kyung Chang, Eun Sun Jung, Myeong-Cherl Kook, So-Young Jin, Yang Seok Chae, Young Soo Park, Mi Seon Kang, Hyunki Kim, Jae Hyuk Lee, Do Youn Park, Kyoung Mee Kim, Hoguen Kim, Young Ju Suh, Sang Yong Seol, Hwoon-Yong Jung, Deuck–Hwa Kim, Na Rae Lee, Seung-Hee Park, Ji Hye You; Cancer Res Treat. 2019;51(4):1568-1577. Published online April 1, 2019; DOI: https://doi.org/10.4143/crt.2019.019

Abstract PDF PubReader ePub

Purpose
The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance.
Materials and Methods
We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions.
Results
The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important.
Conclusion
The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Citations

Citations to this article as recorded by

Seeing the random forest through the decision trees. Supporting learning health systems from histopathology with machine learning models: Challenges and opportunities
Ricardo Gonzalez, Ashirbani Saha, Clinton J.V. Campbell, Peyman Nejat, Cynthia Lokker, Andrew P. Norgan
Journal of Pathology Informatics.2024; 15: 100347. CrossRef
A new, simplified endoscopic scoring system for predicting clinical outcome in gastric low-grade intraepithelial neoplasia: the “e-cout system”
Nanjun Wang, Xiaotong Niu, Longsong Li, Jing Tang, Yawei Bi, Shengzhen Liu, Ke Han, Yaxuan Cheng, Zhaobei Cai, Ningli Chai, Enqiang Linghu
Neoplasia.2024; 56: 101030. CrossRef
A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy
Yu Han Zhao, Yu Zheng, Jie Sha, Hong Jin Hua, Ke Dong Li, Yu Lu, Yi Ni Dang, Guo Xin Zhang
Gut and Liver.2023; 17(1): 78. CrossRef
A standardized pathology report for gastric cancer: 2nd edition
Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
Journal of Pathology and Translational Medicine.2023; 57(1): 1. CrossRef
Tumor heterogeneity and carcinoma in resected specimens of gastric low-grade dysplasia: A retrospective single center study
Ga-Yeong Shin, Jun Young Park, Sung Hak Lee, Yu Kyung Cho, Myung-Gyu Choi, Jae Myung Park, Alessandro Rizzo
PLOS ONE.2023; 18(1): e0280735. CrossRef
A Standardized Pathology Report for Gastric Cancer: 2nd Edition
Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
Journal of Gastric Cancer.2023; 23(1): 107. CrossRef
Accuracy of administrative claim data for gastric adenoma after endoscopic resection
Ga-Yeong Shin, Hyun Ho Choi, Jae Myung Park, Sang Yoon Kim, Jun Young Park, Donghoon Kang, Yu Kyung Cho, Sung Soo Kim, Myung-Gyu Choi
Clinical Endoscopy.2023; 56(3): 325. CrossRef
Artificial Intelligence in the Pathology of Gastric Cancer
Sangjoon Choi, Seokhwi Kim
Journal of Gastric Cancer.2023; 23(3): 410. CrossRef
Establishment and validation of a clinical diagnostic model for gastric low-grade intraepithelial neoplasia
Ting Sun, Xi-quan Ke, Meng Wang, Qi-zhi Wang
Medicine.2023; 102(46): e35515. CrossRef
Assessment of deep learning assistance for the pathological diagnosis of gastric cancer
Wei Ba, Shuhao Wang, Meixia Shang, Ziyan Zhang, Huan Wu, Chunkai Yu, Ranran Xing, Wenjuan Wang, Lang Wang, Cancheng Liu, Huaiyin Shi, Zhigang Song
Modern Pathology.2022; 35(9): 1262. CrossRef
Deep learning for automatic diagnosis of gastric dysplasia using whole-slide histopathology images in endoscopic specimens
Zhongyue Shi, Chuang Zhu, Yu Zhang, Yakun Wang, Weihua Hou, Xue Li, Jun Lu, Xinmeng Guo, Feng Xu, Xingran Jiang, Ying Wang, Jun Liu, Mulan Jin
Gastric Cancer.2022; 25(4): 751. CrossRef
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Joaquín Cubiella, Ángeles Pérez Aisa, Miriam Cuatrecasas, Pilar Díez Redondo, Gloria Fernández Esparrach, José Carlos Marín-Gabriel, Leticia Moreira, Henar Núñez, M. Luisa Pardo López, Enrique Rodríguez de Santiago, Pedro Rosón, José Miguel Sanz Anquela,
Gastroenterología y Hepatología.2021; 44(1): 67. CrossRef
Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP
Joaquin Cubiella, Ángeles Pérez Aisa, Miriam Cuatrecasas, Pilar Díez Redondo, Gloria Fernández Esparrach, José Carlos Marín-Gabriel, Leticia Moreira, Henar Núñez, M. Luisa Pardo López, Enrique Rodríguez de Santiago, Pedro Rosón, José Miguel Sanz Anquela,
Gastroenterología y Hepatología (English Edition).2021; 44(1): 67. CrossRef

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254 Download
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Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors: Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang; Cancer Res Treat. 2018;50(3):835-842. Published online August 29, 2017; DOI: https://doi.org/10.4143/crt.2017.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
Materials and Methods
Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
Results
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
Conclusion
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.

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Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters: The Gastrointestinal Pathology Study Group of Korean Society of Pathologists, Jin Hee Sohn, Mee-Yon Cho, Yangsoon Park, Hyunki Kim, Woo Ho Kim, Joon Mee Kim, Eun Sun Jung, Kyoung-Mee Kim, Jae Hyuk Lee, Hee Kyung Chan, Do Youn Park, Mee Joo, Sujin Kim, Woo Sung Moon, Mi Seon Kang, So-Young Jin, Yun Kyung Kang, Sun Och Yoon, HyeSeung Han, EunHee Choi; Cancer Res Treat. 2015;47(4):813-822. Published online February 26, 2015; DOI: https://doi.org/10.4143/crt.2014.238

Abstract PDF PubReader ePub

Purpose
In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. Materials and Methods A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped.
Results
In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. Conclusion From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

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Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis: Yun-Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae-Su Han, Hye Seong Ahn, Seong-Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang; Cancer Res Treat. 2015;47(4):718-726. Published online February 2, 2015; DOI: https://doi.org/10.4143/crt.2014.064

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis.
Materials and Methods
Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse- transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, and tissue- microarray (TMA) comprising 47 AGC patients.
Results
CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI- 1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393).
Conclusion
DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.

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Wei Cheng, Yonghui Liao, Yuan Xie, Qinrong Wang, Leilei Li, Yuanjia Chen, Yan Zhao, Jianjiang Zhou
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p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors: Hee Sung Kim, Hye Seung Lee, Kyung Han Nam, Jiwoon Choi, Woo Ho Kim; Cancer Res Treat. 2014;46(4):383-392. Published online July 17, 2014; DOI: https://doi.org/10.4143/crt.2013.102

Abstract PDF PubReader ePub

Purpose
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous disease group originating from the neuroendocrine cells. Identification of prognostic markers, related to neuroendocrine tissue-selective tumorigenesis, is necessary to find therapeutic targets.
Materials and Methods
A total of 327 patients with GEP-NETs were included in this study; there were 49 gastric, 29 duodenal, 49 pancreatic, 12 hepatobiliary, 33 appendiceal, 5 proximal colon, and 150 distal colon cases. We performed immunostaining with the tissue microarray method for menin, p27, and p18.
Results
We observed negative staining for menin, p27, and p18 in 34%, 21%, and 56% of GEP-NETs, respectively. The loss of p27, but not menin, was positively correlated with the grade of Ki-67. Menin–/p27–, menin–/p27+, menin+/p27–, and menin+/p27+ phenotype groups included 13%, 22%, 8%, and 57% of patients, respectively. A dichotomized comparison showed that menin– or p27– tumors were significantly associated with foregut and midgut localizations, high World Health Organization (WHO) grade, lymph node metastasis, and more advanced stage as compared to menin+/p27+ patients. Kaplan-Meier analysis for the overall survival showed that p27 loss was significantly associated with decreased survival. Multivariate analysis showed that p27 loss is an independent factor for poor overall survival.
Conclusion
Our results revealed that the loss of p27 is associated with poor prognosis and the menin-p27 pathway is important in the tumorigenesis of GEP-NETs.

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Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study: Mee-Yon Cho, Joon Mee Kim, Jin Hee Sohn, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Hyunki Kim, Myeong-Cherl Kook, Do Youn Park, Jae Hyuk Lee, HeeKyung Chang, Eun Sun Jung, Hee Kyung Kim, So-Young Jin, Joon Hyuk Choi, Mi Jin Gu, Sujin Kim, Mi Seon Kang, Chang Ho Cho, Moon-Il Park, Yun Kyung Kang, Youn Wha Kim, Sun Och Yoon, Han Ik Bae, Mee Joo, Woo Sung Moon, Dae Young Kang, Sei Jin Chang; Cancer Res Treat. 2012;44(3):157-165. Published online September 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.3.157

Abstract PDF PubReader ePub

PURPOSE
As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
MATERIALS AND METHODS
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
RESULTS
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
CONCLUSION
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

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Review Article

Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea: Yoon-Koo Kang, Hye Jin Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang; Cancer Res Treat. 2012;44(2):85-96. Published online June 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.2.85

Abstract PDF PubReader ePub

Despite their rarity in incidence and prevalence, gastrointestinal stromal tumors (GISTs) have emerged as a distinct and noteworthy pathogenetic entity. The clinical management of GISTs has rapidly evolved due to the recent elucidation of their oncogenic signal transduction pathway and the introduction of molecular-targeted therapies. Successful management of GISTs requires a multidisciplinary approach firmly based on an accurate histopathologic diagnosis. In 2007, the Korean GIST study group published the first guideline for optimal diagnosis and treatment of GISTs in Korea. The second version of the guideline was published in 2010. Herein, we provide the results of relevant clinical studies for the purpose of further revision to the guideline. We expect this new guideline will enhance the accuracy of diagnosis, as performed by members of the Korean associate of physicians involved in GIST patient care, thus improving the efficacy of treatment.

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Original Articles

Expression of BamHI-A Rightward Transcripts in Epstein-Barr Virus-Associated Gastric Cancers: Bo-Gun Jang, Eun Ji Jung, Woo Ho Kim; Cancer Res Treat. 2011;43(4):250-254. Published online December 27, 2011; DOI: https://doi.org/10.4143/crt.2011.43.4.250

Abstract PDF PubReader ePub

PURPOSE
About 10% of all gastric cancers (GCs) are Epstein-Barr virus (EBV)-associated. However, the oncogene of EBV in gastric carcinogenesis has not yet been established. In the present study, we investigated the virus-derived transcripts in the EBV-infected GC cell line to explore the viral oncogene of EBV-positive GCs.
MATERIALS AND METHODS
We used the SNU719 cell line, a naturally derived EBV-infected GC cell line. The individual expressed sequence tags from the cDNA libraries of SNU719 were searched against the mRNA subset extracted from the GenBank data base. Sequence reaction was carried out for the EBV-associated clones. Reverse transcription-polymerase chain reaction was performed after cells were partitioned into nuclear and cytoplasmic fractions.
RESULTS
Using bioinformatic tools, we selected 13 EBV-associated clones from cDNA libraries of SNU719. By sequencing analysis, we revealed that they were all associated with RPMS1, one of the BamHI-A rightward transcripts (BART) of EBV. Some BART cDNAs such as RPMS1 and A73 are known to be translated into protein in vitro, and have been shown to have some biochemical functions relevant to tumorigenesis. But, presently, the BART transcripts were expressed only in the nucleus and not in the cytoplasm, arguing against their role as messenger RNAs. Some other BART transcripts expressed in GCs (BARF0, CST, vIL, BARF1, BLLF1, and BcLF1) were also extensively detected in the nucleus.
CONCLUSION
BART transcripts are the predominant viral transcripts expressed in EBV-associated GCs, and they are located only in the nucleus. Therefore, it seems less likely that BART transcripts produce functional proteins to play a role in carcinogenesis of EBV-associated GCs.

Citations

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Role of BamHI-A Rightward Frame 1 in Epstein–Barr Virus-Associated Epithelial Malignancies
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MAMTA KALRA, ULRIKE GERDEMANN, JESSICA D. LUU, MINTHRAN C. NGO, ANN M. LEEN, CHRYSTAL U. LOUIS, CLIONA M. ROONEY, STEPHEN GOTTSCHALK
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Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors: Hee Sung Kim, Hye Seung Lee, Woo Ho Kim; Cancer Res Treat. 2011;43(3):181-188. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.181

Abstract PDF PubReader ePub

PURPOSE
This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
MATERIALS AND METHODS
Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5.
RESULTS
COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001).
CONCLUSION
Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.

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Case Report

A Case of Desmoplastic Small Round Cell Tumor Diagnosed in a Young Female Patient: Ji-Won Kim, Jin Hyun Park, Hyeon Jin Cho, Ji-Hyun Kwon, Youngil Koh, Su-Jung Kim, Se Hyung Kim, Se-Hoon Lee, Seock-Ah Im, Yong-Tae Kim, Woo Ho Kim; Cancer Res Treat. 2009;41(4):233-236. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.233

Abstract PDF PubReader ePub

Desmoplastic small round cell tumor is a very rare malignancy. We report the case of a 26-year-old woman who suffered from dyspepsia and abdominal pain for 2 months. We performed an endoscopic biopsy of the duodenal mass and diagnosed her disease as desmoplastic small round cell tumor using immunohistochemical staining, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction. Because the mass invaded the pancreas and superior mesenteric vein as well as duodenum and the disease was disseminated to liver and peritoneum, she received palliative chemotherapy using vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. The maximal response to chemotherapy was stable disease. The patient expired 9 months after diagnosis.

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Review Articles

Tissue Array Methods for High-throughput Clinicopathologic Research: Hye Seung Lee, Woo Ho Kim; Cancer Res Treat. 2006;38(1):1-6. Published online February 28, 2006; DOI: https://doi.org/10.4143/crt.2006.38.1.1

Abstract PDF PubReader ePub

Recent research in molecular biology has identified a significant number of novel markers, which may have diagnostic, prognostic and therapeutic significance. High-throughput tissue array method facilitates the validation of novel markers by enabling the simultaneous analysis of hundreds or thousands of tissue specimens. Tissue array slides can be analyzed using techniques such as immunohistochemistry and in situ hybridization. In this review, we give a brief overview of tissue array method and its application to high throughput clinicopathologic research.

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Epstein-Barr Virus in Human Malignancy: A Special Reference to Epstein-Barr Virus associated Gastric Carcinoma: Mee Soo Chang, Woo Ho Kim; Cancer Res Treat. 2005;37(5):257-267. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.257

Abstract PDF PubReader ePub

Epstein-Bar virus (EBV), a human herpesvirus, establishes a life-long persistent infection in 90~95% of human adult population worldwide. EBV is the etiologic agent of infectious mononucleosis, and EBV is associated with a variety of human malignancy including lymphoma and gastric carcinoma. Recently, EBV has been classified as group 1 carcinogen by the WHO International Agency for Research on Cancer. Evidence is presented which suggests that failures of the EBV-specific immunity may play a role in the pathogenesis of EBV-associated malignancy. At present, the precise mechanisms by which EBV transforms B lymphocytes have been disclosed. Encouragingly, they have had enough success so far to keep them enthusiastic about novel therapeutic trial in the field of EBV-associated lymphoma. However, information on EBV-associated gastric carcinoma is still at dawn. This article reviews EBV biology, immunological response of EBV infection, unique oncogenic property of EBV, peculiarity of EBV-associated gastric carcinoma, and lastly, EBV-targeted therapy and vaccination.

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Original Articles

Loss of DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs) Expression in Gastric Cancers: Hye Seung Lee, Han-Kwang Yang, Woo Ho Kim, Gheeyoung Choe; Cancer Res Treat. 2005;37(2):98-102. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.98

Abstract PDF PubReader ePub

Purpose

DNA-PKcs is one of the DNA repair genes. It was recently found that hyperplasia and dysplasia of the intestinal mucosa and the production of aberrant crypt foci were developed in DNA-PKcs-null mice, and this suggests a suppressive role for DNA-PKcs in tumorigenesis.

Materials and Methods

To investigate the possible relationship between the clinico-pathologic characteristics and the survival of gastric cancer patients, the expression status of DNA-PKcs was determined in 279 consecutive gastric cancers. Immunohistochemical analysis was performed to evaluate the expression levels of DNA-PKcs protein by using the tissue array method.

Results

Out of 279 consecutive gastric cancers, 63 cases (22.6%) showed the loss of DNA-PKcs expression. The loss of DNA-PKcs expression was significantly associated with advanced cancer (p<0.001), lymphatic invasion (p=0.001), lymph node metastasis (p=0.009), and advanced pTNM stage (p=0.009). Univariate survival analysis revealed that patients with the loss of DNA-PKcs expression had significantly poorer survival than those patients with intact DNA-PKcs expression (p=0.004). Moreover, the loss of DNA-PKcs expression was identified to correlate with a lower survival in the subgroup of stage I gastric cancer patients (p=0.037).

Conclusion

The loss of DNA-PKcs expression was found in 23% of human gastric cancers and this was identified to significantly correlate with poor patient survival, especially for stage I gastric cancer patients.

Citations

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Prognostic Significance of CD24 Expression in Gastric Carcinoma: Nevine S. Darwish, Min A Kim, Mee Soo Chang, Hye Seung Lee, Byung Lan Lee, Yong Il Kim, Woo Ho Kim; Cancer Res Treat. 2004;36(5):298-302. Published online October 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.5.298

Abstract PDF PubReader ePub

Purpose

The human CD24 antigen is a small heavily glycosylated cell surface protein, which is expressed in hematological malignancies, as well as in a large variety of solid tumors. Its expression is now known to be related to the prognosis of several kinds of tumors. This study is designed to examine the prognostic significance of CD24 in Korean gastric cancer patients.

Materials and Methods

In the present study, we examined CD24 expression in 300 consecutive cases of gastric carcinoma by immunohistochemical staining using the tissue-array method. We also investigated the clinicopathological profiles related to CD24 expression.

Results

One hundred and three cases out of 300 (34.3%) showed the positive expression of CD24. The altered expression of CD24 was significantly associated with differentiated cancer (p=0.003), the intestinal subtype according to the Lauren classification (p<0.001), the advanced stage cancer (p=0.027), with lymphatic invasion (p=0.038) and with vascular invasion (p=0.006). The survival analysis revealed that the patients with CD24 positive expression showed significantly poorer survival than those without CD24 expression. Moreover, a combined evaluation revealed that PTEN+/CD24- cases showed the best survival compared to other groups (p=0.01).

Conclusion

Positive CD24 expression occurs in a subset of gastric carcinomas and it correlates significantly with lymphatic invasion, blood vessel invasion and poor survival.

Citations

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Arthritis Research & Therapy.2016;[Epub] CrossRef
CD44v3+/CD24− cells possess cancer stem cell-like properties in human oral squamous cell carcinoma
KEITA TODOROKI, SACHIKO OGASAWARA, JUN AKIBA, MASAMICHI NAKAYAMA, YOSHIKI NAITO, NAOKO SEKI, JINGO KUSUKAWA, HIROHISA YANO
International Journal of Oncology.2016; 48(1): 99. CrossRef
CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation
Yao-An Shen, Chia-Yu Wang, Hui-Yen Chuang, John Jeng-Jong Hwang, Wei-Hsin Chi, Chih-Hung Shu, Ching-Yin Ho, Wing-Yin Li, Yann-Jang Chen
Oncotarget.2016; 7(36): 58351. CrossRef
CD24 Overexpression Is Associated with Poor Prognosis in Luminal A and Triple-Negative Breast Cancer
Mi Jeong Kwon, Jinil Han, Ji Hyun Seo, Kyoung Song, Hae Min Jeong, Jong-Sun Choi, Yu Jin Kim, Seon-Heui Lee, Yoon-La Choi, Young Kee Shin, Yves St-Pierre
PLOS ONE.2015; 10(10): e0139112. CrossRef
Expression of CD24, p21, p53, and c‐myc in alpha‐fetoprotein‐producing gastric cancer: Correlation with clinicopathologic characteristics and survival
Xiaowen Liu, Hongmei Yu, Hong Cai, Yanong Wang
Journal of Surgical Oncology.2014; 109(8): 859. CrossRef
CD24 mediates gastric carcinogenesis and promotes gastric cancer progression via STAT3 activation
Ying-Chao Wang, Ji-Lin Wang, Xuan Kong, Tian-Tian Sun, Hao-Yan Chen, Jie Hong, Jing-Yuan Fang
Apoptosis.2014; 19(4): 643. CrossRef
CD44 but not CD24 expression is related to poor prognosis in non-cardia adenocarcinoma of the stomach
Xueyuan Cao, Donghui Cao, MeiShan Jin, Zhifang Jia, Fei Kong, Hongxi Ma, Yinping Wang, Jing Jiang
BMC Gastroenterology.2014;[Epub] CrossRef
Hypoxia‐mediated CD24 expression is correlated with gastric cancer aggressiveness by promoting cell migration and invasion
Nobuaki Fujikuni, Hideki Yamamoto, Kazuaki Tanabe, Yutaka Naito, Naoya Sakamoto, Yuka Tanaka, Kazuyoshi Yanagihara, Naohide Oue, Wataru Yasui, Hideki Ohdan
Cancer Science.2014; 105(11): 1411. CrossRef
Clinicopathological and Prognostic Significance of CD24 Overexpression in Patients with Gastric Cancer: A Meta-Analysis
Jing-Xun Wu, Yuan-Yuan Zhao, Xuan Wu, Han-Xiang An, Yitao Ding
PLoS ONE.2014; 9(12): e114746. CrossRef
Biomarkers for predicting future metastasis of human gastrointestinal tumors
Lui Ng, Ronnie Tung Ping Poon, Roberta Pang
Cellular and Molecular Life Sciences.2013; 70(19): 3631. CrossRef
CD44/CD24 Expression in recurrent gastric cancer: a retrospective analysis
Ching-Shya Yong, Chih-Ming Ou Yang, Yenn-Hwei Chou, Chao-Sheng Liao, Chung-Wei Lee, Chin-Cheng Lee
BMC Gastroenterology.2012;[Epub] CrossRef
PTEN deletion is rare but often homogeneous in gastric cancer
Sormeh Mina, Benjamin A Bohn, Ronald Simon, Antje Krohn, Matthias Reeh, Dirk Arnold, Carsten Bokemeyer, Guido Sauter, Jakob R Izbicki, Andreas Marx, Phillip R Stahl
Journal of Clinical Pathology.2012; 65(8): 693. CrossRef
Prognostic significance of loss of c-fos protein in gastric carcinoma
Seon Pil Jin, Ji Hun Kim, Min A Kim, Han-Kwang Yang, Hee Eun Lee, Hye Seung Lee, Woo Ho Kim
Pathology & Oncology Research.2007; 13(4): 284. CrossRef
Tissue Array Methods for High-throughput Clinicopathologic Research
Hye Seung Lee, Woo Ho Kim
Cancer Research and Treatment.2006; 38(1): 1. CrossRef
Loss of DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs) Expression in Gastric Cancers
Hye Seung Lee, Han-Kwang Yang, Woo Ho Kim, Gheeyoung Choe
Cancer Research and Treatment.2005; 37(2): 98. CrossRef
Cytoplasmic CD24 Expression in Colorectal Cancer Independently Correlates with Shortened Patient Survival
Wilko Weichert, Carsten Denkert, Mick Burkhardt, Tserenchunt Gansukh, Joachim Bellach, Peter Altevogt, Manfred Dietel, Glen Kristiansen
Clinical Cancer Research.2005; 11(18): 6574. CrossRef

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Prognostic Significance of Lymph Node Micrometastasis in pT2N0 Gastric Cancer: Hyeon Kook Lee, Sam Je Cho, Yoon Ho Kim, Hye Seung Lee, Woo Ho Kim, Kuhn Uk Lee, Kuk Jin Choe, Jin Pok Kim, Han Kwang Yang; J Korean Cancer Assoc. 2001;33(2):130-135.

Abstract PDF: PURPOSE
The prognostic significance of lymph node (LN) micrometastasis in gastric cancer remains contro versial. We therefore investigated the clinicopathologic factors related to LN micrometastasis and evaluated the clinical relevance of micrometastasis with regard to urrence.
MATERIALS AND METHODS
A total of 1083 LNs from 39 patients with pT2N0 gastric cancer and who underwent curative resection in 1993 were further immunohistochemically stained using an anti-cytokeratin Ab cocktail (AE1-AE3).
RESULTS
Micrometastases were found in 3.9% (42/1083) of the resected LNs and 53.8% (21/39) of the patients with pT2N0 gastric cancer. LN micrometastasis was found to be significantly related with histologic differentiation. The recurrence rate of gastric cancer was higher in patients with LN micrometastasis (31.6%) than in those without (6.3%), with a borderline significance (p=0.074). In uni variate analysis, patients with LN micrometastasis had a shorter 5-year disease-free survival (65%) than those without LN micrometastasis (87%) (p=0.075). In multivariate analysis, multiple LN micrometastasis was associated with a poor prognosis, but with a borderline significance (p=0.069, Risk ratio 4.815) CONCLUSION: We were able to identify LN micrometastases missed on routine H-E staining, using an immuno histochemical technique. Our results suggest that LN micrometastasis is associated with the recurrence of pT2N0 gastric cancer.

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Clinical Significance of p53, c-erbB-2, Chromogranin A and PCNA in the Ampullary Carcinoma: Ki Hwan Kim, Sun Whe Kim, Woo Ho Kim, Yong Hyun Park; J Korean Cancer Assoc. 2001;33(1):84-91.

Abstract PDF: PURPOSE
To determine the clinical significance of p53, c-erbB-2, chromogranin A (CgA), proliferating cell nuclear antigen (PCNA) expression in ampullary carcinoma, a retrospective study was performed.
MATERIALS AND METHODS
The cases of 96 patients who underwent curative resection for ampullary carcinoma during the ten-year period (1986-95) were reviewed. And, using paraffin-embedded tumor tissues, immunohistochemical (IHC) staining for p53, c-erbB-2, CgA, and PCNA was performed.
RESULTS
The overall five-year survival rate (5-YSR) for these 96 patients was 58%. With regard to TNM stage, the 5-YSR was 71% for stage I (n=36), 62% for stage II (n=29), and 39% for stage III (n=31), respectively. IHC expression rate was 17.6% for c-erbB-2, 19.2% for CgA, and 42.9% for p53. The relative proportion of labelling index of PCNA (<25%, 25-50%, >50%) was 30.8%, 25.3%, and 44.0%, respectively. The PCNA labelling index showedsignificant correlation with tumor size (p=0.032). The PCNA labelling index, c-erbB-2, CgA and p53 were not correlated to extent of invasion, lymph node metastasis, stage, or histologic type. CgA and c-erbB-2 expression and the PCNA labelling index thus had no prognostic value. With regard to p53, the 5-YSR of p53 negative cases was 68.6%; that of p53 positive cases was 47%, with significant difference (p=0.038).
CONCLUSION
This result suggests that p53 expression is related to poor prognosis of ampullary carcinoma, and that c-erbB-2 and CgA expression, and the PCNA labelling index, are not significant prognostic factors.

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K-ras Mutation in Ampulla of Vater Cancer: Sang Jae Park, Sun Whe Kim, Woo Ho Kim, Jin Young Jang, Yong Hyun Park; J Korean Cancer Assoc. 2000;32(5):981-988.

Abstract PDF: PURPOSE
The aims of this study was to elucidate the role of the K-ras mutation (codon 12) in the carcinogenesis of ampulla of Vater cancer.
MATERIALS AND METHODS
31 cases of radically resected ampullary cancer cases were enrolled. 18 cases harbored the adenomatous portions adjacent to carcinomatous portions. Utilizing a two-step nested PCR with RFLP method, we examined the K-ras mutation in a total of 90 samples (normal mucosas (N=31), carcinomatous portions (N=31), adenomatous portions (N=18), and metastatic lymph nodes (N=10)).
RESULTS
In the carcinomatous portion, K-ras mutations in codon 12 were detected in 48.4%. In the adenomatous portions, 10 cases (55.6%) out of 18 displayed the K-ras mutation. In the metastatic lymph nodes, K-ras mutation was found in 4 cases out of 10. After sequencing, 4 mutant types (GTT, GAT, GCT and TGT) of codon 12 (normally GGT) in the ampulla of Vater cancer were detected and the mutated types in the adenomatous portions, carcinomatous portions and metastatic lymph nodes in the same cases were identical. CONCLUSION: The presence of concomitant K-ras mutation in both the adenomatous and carcinomatous portions in some cases may suggest the role of K-ras mutation in the early carcinogenesis of ampulla of Vater cancer.

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Sequential Changes of Proliferative Fraction of Enzyme Altered Fdegrees Ci in Experimental Rat Hepatdegrees Carcinogenesis: Woo Ho Kim, Yun Sil Yoo, Yong Il Kim, Mi Sook Lee, Min Jae Lee, Ja June Jang; J Korean Cancer Assoc. 2000;32(3):563-570.

Abstract PDF: PURPOSE
The proliferative activity of cells in enzyme altered fdegrees Ci of the rat hepatoma model was measured by double immunohistdegrees Chemical staining methods using anti-bromodeoxyuridine (BrdU) and anti-glutathione S transferase of placental form (GST-P). The aim of this study was to compare the cell proliferative activity in GST-P positive altered fdegrees Ci and in negative fdegrees Ci.
MATERIALS AND METHODS
Eight-week-old male Sprague-Dawley rats were administered by 200 mg/kg diethylnitrosamine (DEN) intraperitoneally, and followed by 0.02% acetylaminofluorene (AAF)-containing diet for 4 weeks. One week after administration of AAF diet, two-thirds hepa tectomy was performed. Control animals were treated as same except for the omission of AAF in the diet. The rats were sacrified 0, 1, 3, 5, 7, 14 and 21 days after partial hepatectomy. The slices of liver were fixed in acetone, dehydrated in benzene and stained by peroxidase-anti peroxidase method against GST-P and by avidine-biotin peroxidase complex method against BrdU.
RESULTS
The area of the GST-P positive fdegrees Ci was increased during the experimental period. In the experimental group, the S-phase fraction in the fdegrees Ci remained high during the first week and was decreased thereafter. However, the GST-P negative area maintained a low S-phase cell frac tion throughout the experimental period.
CONCLUSION
These results suggest that hepatic cells in the enzyme altered fdegrees Ci may escape a suppressor effect of AAF in contrast to the normal cells in which their growth are inhibited by AAF.

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Expression of p53, p21/WAF1, bcl-2 and Loss of Heterozygosity for the Study of Apoptosis in Gastric Carcinoma: Hang Jong Yu, Joo Ho Lee, Woo Ho Kim, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(3):447-457.

Abstract PDF: PURPOSE
The purpose of this study was to correlate the immunohistdegrees Chemical expressions of p53, p21 and bcl-2, with their loss of heterozygosity (LOH) and clinical significance.
MATERIALS AND METHODS
Paraffin-embedded tissue sections from 30 patients with gastric car cinomas were examined for immunohistdegrees Chemical staining and LOH study. Primary antibodies used in immunohistdegrees Chemical staining were mouse mondegrees Clonal antibody to human p53, p21/ WAF1 and bcl-2. For PCR-LOH assays, D6S271, D6S105, D18S386, TP53, D17S796, and D17S786 microsatellite markers were used.
RESULTS
The expression rates of p53, p21 and bcl-2 were 76.7%, 80% and 3.3%, respectively. The expression of p21 was correlated with lymph node metastasis. LOH were found in 20.8% at D6S271, 42.3% at D6S105, 31.6% at D18S386, 39.1% at TP53, 40.9% at D17S796, and 50.0% at D17S786. No correlation was found between the immunohistdegrees Chemical expression and the LOH in these gene sites.
CONCLUSION
p53 and p21 were detected in high rate, whereas bcl-2 expression rate was very low in gastric adendegrees Carcinoma. Of them, overexpression of p21 was correlated with the tumor progression. High incidence rate of LOH may play an important role in gastric carcinogenesis. These findings suggest that the effects on apoptosis and cell cycle by p53 and p21 were important in development and progression of gastric cancer.

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Clinicopathologic Characteristics and p53, c-erbB2, nm23 Protein Expression in Gastric Remnant Cancer: Joo Ho Lee, Yoe Kyu Youn, Woo Ho Kim, Hang Jong Yu, Byoung Jo Suh, Han Kwang Yang, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(1):26-37.

Abstract PDF: PURPOSE
The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer.
MATERIALS AND METHODS
We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23.
RESULTS
The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC.
CONCLUSION
Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.

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The Incidence of Hereditary Gastric Cancer in Korean: Soo Jin Kim, Sam Je Cho, Seung Chul Heo, Han Kwang Yang, Woo Ho Kim, Jae Gahb Park, Kuhn Uk Lee, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(1):1-6.

Abstract PDF: PURPOSE
We wanted to determine the incidence of HGC (hereditary gastric cancer) in Korean under the minimal criteria of ICG-HGC (International Collaborative Group on Hereditary Gastric Cancer).
MATERIALS AND METHODS
Tumor registry abstracts of 1752 patients who underwent operations for gastric cancer during the time period 1996 to 1998 in the Department of Surgery at Seoul National University College of Medicine were examined. Based on their family histories, candidate HGCs were identified. Their detailed family histories including diagnosis of cancer, age at diagnosis, and dates of birth and death were obtained from interviews by phone. Another study was performed on 195 patients with gastric cancer who admitted for operations in the same department during the time period April, 1999 to June, 1999. Their detailed family histories were also obtained from probands or nearest relatives during admission. Pedigree studies of documented families were conducted. Minimal Criteria of ICG-HGC we used for present study are as followings: At least three relatives with histologically verified gastric cancer; one of them should be a first-degree relative to the other two. At least two successive generations should be affected. In one of the relatives, gastric cancer should be diagnosed under 45 years of age. Suspected HGC fullfills only two of the above three criteria. HNPCC, FAP and Li-Fraumeni syndromes should be excluded.
RESULTS
A total of 12 HGCs were identified in this study. In recent 3 years, during the time period 1996 to 1998, the incidence of true and suspected HGC accounted for 6 (0.3%) and 44 probands (2.5%) among 1752 patients (in 1996, 0.4% and 3.2%; in 1997, 0.3% and 1.8%; in 1998, 0.3% and 2.8%) respectively. In contrast, during the time period April, 1999 to June, 1999, the incidence of true and suspected HGC increased up to 3.1% (6 probands) and 11.3% (22 probands), respectively, out of 195 patients (in April, 1999, 0% and 11.7%; in May, 1999, 4% and 14.7%; in June, 1999, 5% and 6.7%). There was no difference in terms of the incidence even if the third criterion of age at diagnosis among Minimal Criteria of ICG-HGC was modified from 'under 45 years of age' to 50. Mean ages of 12 probands (46.3 8.8) were statistically younger than those of control gastric cancer patients (54.2 11.5) retrieved from database of Department of Surgery at Seoul National University College of Medicine.
CONCLUSION
In the present study, the incidences of HGC were remarkably altered in accordance with study methods. Retrospective reviews of medical records revealed to be ineffective for this kind of study since their informations were often incomplete and some suspected patients were lost during follow-up. According to the Minimal Criteria of ICG-HGC, the incidence of true and suspected HGC was 3.1% (6 probands) and 11.3% (22 probands), respectively, out of 195 gastric cancer patients. We propose that families who meet the Minimal Criteria of ICG-HGC should be prospectively found in order to determine the exact incidence of HGC in Korean.

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Effects of Wild - type p53 Gene Transfection into Human Colon Cancer Cell Line: Hyun Ok Kim, Woo Ho Kim, Soo In Bae, He Won Lee, Chong Jai Kim, Sung Youl Hong, Yong Il Kim; J Korean Cancer Assoc. 1999;31(2):367-376.

Abstract PDF: PURPOSE
In colon cancer, the most frequent genetic alteration is found in p53 tumor suppressor gene residing on the short arm of chromosome 17. In order to investigate the significance of wild-type p53, we transfected wild type p53 into human colon cancer cell lines and analysed tbeir biologic effects.
MATERIALS AND METHODS
For analysis of p53 status in cell lines, polymerase chain reaction-single stranded confonnation polymorphism (PCR-SSCP), PCR-direct sequencing and Western blot analysis were employed. Transient transfection with liposome-p53 complex was followed by cell biologic assay.
RESULTS
We found that twelve of fifteen human colon cancer cell lines showed mutation of p53 by PCR-SSCP method. These results almost corresponded to p53 protein accumulations assessed by Westem blot using PAbl801. After transfection with lipafect- AMINE and wild type p53 complex on p53 mutant type cell line (LS1034), viability was reduced to 17.9%, and invasiveness was reduced to 37.3%. Morphologically, wild type p53 transfected cells showed lumen formation and apoptosis after induction of differentiation by Matrigel.
CONCLUSION
Wild type p53 transfection into p53 mutated colon cancer ceil line resulted in restoration of tumor suppressor effect of p53, and this model would be one of the experimental systems for p53-based gene therapy.

3,089 View
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Expression of EGF Receptor Family Genes and Proteins in Gastric Cacner ( EGFR , c-erbB-2 , c-erbB-3 , c-erbB-4 ): Hae Wan Lee, Eun Young Choi, Chang Dae Bae, Han Kwang Yang, Woo Ho Kim, Jin Pok Kim; J Korean Cancer Assoc. 1998;30(5):853-868.

Abstract PDF: PURPOSE
to evaluate the relationship between the expression of EGF receptor gene family and clinico-pathologic parameters.
MATERIALS AND METHODS
We compared adenocarcinoma tissue with normal mucosa obtained from same patients in 60 cases. The amplifications of DNA was examined by slot blot, while the expression of mRNA by ribonuclease protection assay, and that of protein by immunohistochemistry.
RESULTS
Expression of EGFR mRNA was observed in 9 of 59, that of c-erbB-2 mRNA in 8 of 57, that of c-erbB-3 mRNA in 4 of 60, and that of c-erbB-4 mRNA in 13 of 59. The expression of EGFR in expanding type showed a higher tendency than that in infiltrative type. The expression of c-erbB-2 in poorly differentiated adenocarcinoma showed a higher tendency than that in well differentiated adenocarcinoma. And expression of c-erbB-2 was correlated with presence of endolymphatic tumor emboli. No significant correlation was observed between expression of EGFR mRNA and that of its protein or amplification of its DNA. Similarly, No clear relationship between c-erbB-2 gene amplification and expression of mRNA or proteins was detected.
CONCLUSION
EGFR, c-erbB-2, c-erbB-3, and c-erbB-4 were expressed in gastric adenocarcinoma in Korea. The presence of EGF receptor gene family by various tumor cells suggested that it may play an important role in adenocarcinoma. Therefore further studies are currently being carried out to clarify the role of these oncogenes in tumor behavior and gastric carcinogenesis.

2,219 View
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Significance of p53 overexpression in extrahepatic bile duct cancer: Sun Hee Kim, Woo Ho Kim, Yong Hyun Park; J Korean Cancer Assoc. 1993;25(6):873-877.

Abstract PDF: No abstract available.

2,293 View
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Significance of chromogranin-A expression in the bile duct cancer: Sun Whe Kim, Woo Ho Kim, Sam Je Cho, Yong Hyun Park; J Korean Cancer Assoc. 1993;25(4):501-506.

Abstract PDF: No abstract available.

2,278 View
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A study on the cell kinetics of transitional cell carcinoma of the bladder:measurements of DNA content and proliferating cell nuclear antigen: Jong Bok Lee, Jin Soo Jung, Woo Ho Kim, Sang Eun Lee; J Korean Cancer Assoc. 1993;25(3):390-397.

Abstract PDF: No abstract available.

2,144 View
12 Download

Soft tissue sarcoma of extremities: In Mok Jung, Dong Young Roh, Kook Jin Choi, Sang Yong Song, Woo Ho Kim; J Korean Cancer Assoc. 1993;25(2):276-287.

Abstract PDF: No abstract available.

2,041 View
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Effect of sialadenectomy or administration of epidermal growth factor on initiation of hepatoma in rat: Woo Ho Kim, Yong Il Kim; J Korean Cancer Assoc. 1993;25(2):196-201.

Abstract PDF: No abstract available.

1,850 View
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Prognostic significance of epidermal growth factor receptor expression in human gastric carcinoma: Woo Ho Kim, Sang Yong Song, Ki Young Choi, Yong Il Kim, Jin Bok Kim; J Korean Cancer Assoc. 1993;25(1):78-84.

Abstract PDF: No abstract available.

2,723 View
13 Download

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