Cancer Research and Treatment

Original Articles

Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study: Haeryoung Kim, Soyeon An, Kyoungbun Lee, Sangjeong Ahn, Do Youn Park, Jo-Heon Kim, Dong-Wook Kang, Min-Ju Kim, Mee Soo Chang, Eun Sun Jung, Joon Mee Kim, Yoon Jung Choi, So-Young Jin, Hee Kyung Chang, Mee-Yon Cho, Yun Kyung Kang, Myunghee Kang, Soomin Ahn, Youn Wha Kim, Seung-Mo Hong, on behalf of the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists; Cancer Res Treat. 2020;52(1):263-276. Published online July 12, 2019; DOI: https://doi.org/10.4143/crt.2019.192

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Purpose
The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice.
Materials and Methods
Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs.
Results
Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity.
Conclusion
Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

Citations

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Treatment status, survival and gene expression analysis of large-cell neuroendocrine lung carcinoma: a real-world study in China
Fei Qi, Minghang Zhang, Yi Han, Juan Du, Hongjie Yang, Hongmei Zhang, Yong Zhang, Tongmei Zhang
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis
Matteo Tacelli, Manuel Gentiluomo, Paolo Biamonte, Justo P. Castano, Maja Cigrovski Berković, Mauro Cives, Sanja Kapitanović, Ilaria Marinoni, Sonja Marinovic, Ilias Nikas, Lenka Nosáková, Sergio Pedraza-Arevalo, Eleonora Pellè, Aurel Perren, Jonathan Str
Seminars in Cancer Biology.2025; 112: 112. CrossRef
Malignant potential of neuroendocrine microtumor of the pancreas harboring high-grade transformation: lesson learned from a patient with von Hippel-Lindau syndrome
Jongwon Lee, Kyung Jin Lee, Dae Wook Hwang, Seung-Mo Hong
Journal of Pathology and Translational Medicine.2024; 58(2): 91. CrossRef
Rapid Evolution of Metastases in Patients with Treated G3 Neuroendocrine Tumors Associated with NEC-Like Transformation and TP53 Mutation
Atsuko Kasajima, Nicole Pfarr, Eva-Maria Mayr, Ayako Ura, Elisa Moser, Alexander von Werder, Abbas Agaimy, Marianne Pavel, Günter Klöppel
Endocrine Pathology.2024; 35(4): 313. CrossRef
The Complex Histopathological and Immunohistochemical Spectrum of Neuroendocrine Tumors—An Overview of the Latest Classifications
Ancuța-Augustina Gheorghișan-Gălățeanu, Andreea Ilieșiu, Ioana Maria Lambrescu, Dana Antonia Țăpoi
International Journal of Molecular Sciences.2023; 24(2): 1418. CrossRef
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A systematic review of therapeutic strategies in gastroenteropancreatic grade 3 neuroendocrine tumors
Mauro D. Donadio, Ângelo B. Brito, Rachel P. Riechelmann
Therapeutic Advances in Medical Oncology.2023;[Epub] CrossRef
MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus
Tomoyuki Okumura, Tsutomu Fujii, Kenji Terabayashi, Takashi Kojima, Shigeru Takeda, Tomomi Kashiwada, Kazuhiro Toriyama, Susumu Hijioka, Tatsuya Miyazaki, Miho Yamamoto, Shunsuke Tanabe, Yasuhiro Shirakawa, Masayuki Furukawa, Yoshitaka Honma, Isamu Hoshin
Oncology Letters.2023;[Epub] CrossRef
The association between jaundice and poorly differentiated pancreatic neuroendocrine neoplasms (Ki67 index > 55.0%)
Yongkang Liu, Jiangchuan Wang, Hao Zhou, Zicheng Wei, Jianhua Wang, Zhongqiu Wang, Xiao Chen
BMC Gastroenterology.2023;[Epub] CrossRef
An analysis of 130 neuroendocrine tumors G3 regarding prevalence, origin, metastasis, and diagnostic features
Atsuko Kasajima, Björn Konukiewitz, Anna Melissa Schlitter, Wilko Weichert, Günter Klöppel
Virchows Archiv.2022; 480(2): 359. CrossRef
An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms
Tiago Bordeira Gaspar, José Manuel Lopes, Paula Soares, João Vinagre
Endocrine-Related Cancer.2022; 29(12): R191. CrossRef
Solid pancreatic masses in children: A review of current evidence and clinical challenges
Kelli N. Patterson, Andrew T. Trout, Archana Shenoy, Maisam Abu-El-Haija, Jaimie D. Nathan
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Neuroendocrine Carcinomas with Atypical Proliferation Index and Clinical Behavior: A Systematic Review
Tiziana Feola, Roberta Centello, Franz Sesti, Giulia Puliani, Monica Verrico, Valentina Di Vito, Cira Di Gioia, Oreste Bagni, Andrea Lenzi, Andrea M. Isidori, Elisa Giannetta, Antongiulio Faggiano
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Risk of cancer in patients with recurrent aphthous stomatitis in Korea
Ki Jin Kwon, Su Jin Jeong, Young-Gyu Eun, In Hwan Oh, Young Chan Lee
Medicine.2021; 100(16): e25628. CrossRef
Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions
Anna Pellat, Anne Ségolène Cottereau, Lola-Jade Palmieri, Philippe Soyer, Ugo Marchese, Catherine Brezault, Romain Coriat
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Neuroendocrine Carcinomas of the Digestive Tract: What Is New?
Anna Pellat, Anne Ségolène Cottereau, Benoit Terris, Romain Coriat
Cancers.2021; 13(15): 3766. CrossRef
Pancreatic Masses in Children and Young Adults: Multimodality Review with Pathologic Correlation
Lisa Qiu, Andrew T. Trout, Rama S. Ayyala, Sara Szabo, Jaimie D. Nathan, James I. Geller, Jonathan R. Dillman
RadioGraphics.2021; 41(6): 1766. CrossRef
CD56 Expression Is Associated with Biological Behavior of Pancreatic Neuroendocrine Neoplasms

Xin Chen, Chuangen Guo, Wenjing Cui, Ke Sun, Zhongqiu Wang, Xiao Chen
Cancer Management and Research.2020; Volume 12: 4625. CrossRef
Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies
Lingaku Lee, Tetsuhide Ito, Robert T Jensen
Expert Review of Anticancer Therapy.2019; 19(12): 1029. 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

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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

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Poor agreement between biopsies and endoscopic submucosal dissection specimens of Esophageal and Gastric Epithelial Lesions in a western setting
Elisa Cantú-Germano, Glòria Fernández-Esparrach, Alberto Herreros De Tejada, José Carlos Marín-Gabriel, Hugo Uchima, Felipe Ramos-Zabala, Eduardo Albéniz, José Santiago, Oscar Nogales, Enrique Rodríguez De Santiago, Joan B Gornals, Beatriz Peñas, Joaquín
Digestive and Liver Disease.2025;[Epub] CrossRef
An emerging entity of gastric adenocarcinoma: clinicopathological features and differential diagnosis of gastric adenocarcinoma of fundic-gland type in 25 retrospective cases
Chang Zhao, Bo-Jin Su, Wei-Zhen Lin, An-Fang He, Da-Yang Hui, Hai-Ling Liu, Hui Chen, Ming-Ya Xiao, Jian-Ning Chen, Hai-Feng Li, Jin-Yue Zheng, Wei-Jia Wang, Yan Huang, Chun-Kui Shao
Virchows Archiv.2025;[Epub] CrossRef
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
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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,
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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
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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
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Gastroenterología y Hepatología (English Edition).2021; 44(1): 67. CrossRef

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Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers: So Jeong Lee, Cheong-Soo Hwang, Young-Keum Kim, Hyun Jung Lee, Sang-Jeong Ahn, Nari Shin, Jung Hee Lee, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Chang Hun Lee, Gi Young Huh, Mi Young Sol, Hee Jin Lee, Gyungyub Gong, Jee Yeon Kim, Ahrong Kim; Cancer Res Treat. 2017;49(2):313-321. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.098

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Purpose
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers.
Materials and Methods
Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray.
Results
MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor.
Conclusion
High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

Citations

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Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors
Mart van Rijthoven, Simon Obahor, Fabio Pagliarulo, Maries van den Broek, Peter Schraml, Holger Moch, Jeroen van der Laak, Francesco Ciompi, Karina Silina
Communications Medicine.2024;[Epub] CrossRef
The roles of tertiary lymphoid structures in chronic diseases
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Nature Reviews Nephrology.2023; 19(8): 525. CrossRef
NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
Jing Zhang, Mingyue Fan, Chanjuan Jin, Zhaoying Wang, Yutong Yao, Yueru Shi, Xin Hu, Youzhong Wan
Archives of Biochemistry and Biophysics.2022; 727: 109346. CrossRef
Low MxA Expression Predicts Better Immunotherapeutic Outcomes in Glioblastoma Patients Receiving Heat Shock Protein Peptide Complex 96 Vaccination
Yi Wang, Chunzhao Li, Xiaohan Chi, Xijian Huang, Hua Gao, Nan Ji, Yang Zhang
Frontiers in Oncology.2022;[Epub] CrossRef
Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
Abrar I. Aljohani, Chitra Joseph, Sasagu Kurozumi, Omar J. Mohammed, Islam M. Miligy, Andrew R. Green, Emad A. Rakha
Breast Cancer Research and Treatment.2020; 181(3): 541. CrossRef
Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Cancer Research and Treatment.2019; 51(1): 80. CrossRef
Grade II/III Glioma Microenvironment Mining and Its Prognostic Merit
Jiawei Chen, Chongxian Hou, Peng Wang, Yong Yang, Dong Zhou
World Neurosurgery.2019; 132: e76. CrossRef
Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Scientific Reports.2017;[Epub] CrossRef

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Venous Invasion in Colorectal Cancer: Impact of Morphologic Findings on Detection Rate: Chungsu Hwang, Sojeong Lee, Ahrong Kim, Young-Geum Kim, Sang-Jeong Ahn, Do Youn Park; Cancer Res Treat. 2016;48(4):1222-1228. Published online February 12, 2016; DOI: https://doi.org/10.4143/crt.2015.429

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Purpose
Venous invasion (VI) is widely accepted as a poor prognostic factor in colorectal cancer (CRC), and is indicated as a high-risk factor determining the use of adjuvant chemotherapy in CRC. However, there is marked interobserver and intraobserver variability in VI identification and marked variability in the real prevalence of VI in CRC.
Materials and Methods
We investigated the detection rate of VI in 93 consecutive cases of T3 or T4 CRC based on the following: original pathology report, review of hematoxylin and eosin (H&E) slides with attention to the “protruding tongue” and “orphan arteriole” signs, and elastic stain as the gold standard.
Results
Overall, the detection rate of VI was significantly increased as follows: 14/93 (15.1%) in the original pathology report, 38/93 (40.9%) in review of H&E slides with attention to the “protruding tongue” and “orphan arteriole” signs, and 45/93 (48.4%) using elastic stain. VI detection based on morphologic features showed 77.8% sensitivity and 91.1% specificity and showed a linear correlation (Spearman correlation coefficient, 0.727; p < 0.001) with VI detected by elastic stain. In addition, improved agreement between detection methods (detection on the basis of morphologic features, κ=0.719 vs. original pathology report, κ=0.318) was observed using kappa statistics.
Conclusion
Slide review with special attention to the “protruding tongue” and “orphan arteriole” signs could be used for better identification of VI in CRC in routine surgical practice.

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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

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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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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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RImmunohistochemical Evaluation of E-cadherin/catenin (alpha-, beta-, gamma-catenin and p120CTN) Complex Expression in Early Gastric Cancer: Tae Yong Jo, Tae Yong Jeon, Kyu Hwang Chae, Dong Heon Kim, Moon Sup Sim, Do Youn Park, Kang Seuk Suh; Cancer Res Treat. 2003;35(1):16-24. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.16

Abstract PDF

PURPOSE
The significance of abnormal E-cadherin/ catenin complex expression and the correlation of each of its components in cancer remain unclear. This study aimed to characterize the clinical significance of the abnormal membrane expression of the E-cadherin/ catenin complex and the localization patterns of the beta- catenin and p120CTN in early gastric cancer. MATERIALS AND METHODS: Immunohistochemical staining for E-cadherin, alpha-, beta- and gamma-catenin and p120CTN were performed on 47 early gastric cancer specimens. The patterns of membrange expression of the E-cadherin/catenin complex, and the localization patterns of the beta-catenin and p120CTN, were semi quantitatively graded as loss, reduced, preserved or negative and positive. RESULTS: An abnormal immunoreactivity of at least one of E-cadherin/catenin complex proteins was noted in 46 (97.8%) of the 47 early gastric cancer cases. There were no significant correlations of the membrane E-cadherin/catenin expression with, either, sex, age, location, size, macroscopic type, depth of invasion or lymphovascular invasion. Abnormal expressions of membrane E-cadherin, beta-catenin and gamma-catenin were more frequent in the diffuse-type than in the intestinal type. No linear correlation was shown for the beta-catenin between the membrane and cytoplasmic expressions. Nuclear staining of the beta-catenin was observed in 5 (10.6%) cases, but nuclear staining of the p120CTN, a promotor of Kaiso transcriptional factor, was not seen. CONCLUSION: These results suggest that alterations of the E-cadherin/catenin complex may be involved in the early stages of gastric cancer. Although beta-catenin functions as a transcriptional factor, the inactivation of membrane E-cadherin does not appear to result in significant increases in the level of cytoplasmic beta-catenin. Kaiso transcriptional factor may not be involved in the early carcinogenesis of gastric cancer.

Citations

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