Cancer Research and Treatment

Original Article

Gastrointestinal cancer

A Multi-cohort Study of the Prognostic Significance of Microsatellite Instability or Mismatch Repair Status after Recurrence of Resectable Gastric Cancer: Ji Yeong An, Yoon Young Choi, Jeeyun Lee, Woo Jin Hyung, Kyoung-Mee Kim, Sung Hoon Noh, Min-Gew Choi, Jae-Ho Cheong; Cancer Res Treat. 2020;52(4):1153-1161. Published online May 4, 2020; DOI: https://doi.org/10.4143/crt.2020.173

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Purpose
High microsatellite instability (MSI) is related to good prognosis in gastric cancer. We aimed to identify the prognostic factors of patients with recurrent gastric cancer and investigate the role of MSI as a prognostic and predictive biomarker of survival after tumor recurrence.
Materials and Methods
This retrospective cohort study enrolled patients treated for stage II/III gastric cancer who developed tumor recurrence and in whom the MSI status or mismatch repair (MMR) status of the tumor was known. MSI status and the expression of MMR proteins were evaluated using polymerase chain reaction and immunohistochemical analysis, respectively.
Results
Of the 790 patients included, 64 (8.1%) had high MSI status or MMR deficiency. The tumor-node-metastasis stage, type of recurrence, Lauren classification, chemotherapy after recurrence, and interval to recurrence were independently associated with survival after tumor recurrence. The MSI/MMR status and receiving adjuvant chemotherapy were not associated with survival after recurrence. In a subgroup analysis of patients with high MSI or MMR-deficient gastric cancer, those who did not receive adjuvant chemotherapy had better treatment response to chemotherapy after recurrence than those who received adjuvant chemotherapy.
Conclusion
Patients with high MSI/MMR-deficient gastric cancer should be spared from adjuvant chemotherapy after surgery, but aggressive chemotherapy after recurrence should be considered. Higher tumor-node-metastasis stage, Lauren classification, interval to recurrence, and type of recurrence are associated with survival after tumor recurrence and should thus be considered when establishing a treatment plan and designing clinical trials targeting recurrent gastric cancer.

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Special Article

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor: Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang; Cancer Res Treat. 2016;48(4):1155-1166. Published online June 24, 2016; DOI: https://doi.org/10.4143/crt.2016.187

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

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Original Articles

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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Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors
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Scientific Reports.2024;[Epub] CrossRef
The Clinicopathological Significance of Tumor Cell Subtyping in Appendiceal Neuroendocrine Tumors: A Series of 135 Tumors
Ozgur Mete, David W. Dodington, Daniel L. Shen, Sylvia L. Asa
Endocrine Pathology.2024; 35(2): 107. CrossRef
Cauda Equina Neuroendocrine Tumors
Sylvia L. Asa, Ozgur Mete, Ulrich Schüller, Biswarathan Ramani, Kanish Mirchia, Arie Perry
American Journal of Surgical Pathology.2023; 47(4): 469. CrossRef
Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future
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Clinicopathologic Impact of Peptide Hormonal Expression in Rectal Neuroendocrine Tumors
Jisup Kim, Dong-Hoon Yang, HaeSung Jung, HyungJun Cho, Hyeung-Jin Jang, Changhoon Yoo, In Ja Park, Baek-Yeol Ryoo, Jin-Sook Ryu, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2023; 147(7): 797. CrossRef
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Gastroenteropancreatic Neuroendocrine Tumors with Liver Metastases in Korea: A Clinicopathological Analysis of 72 Cases in a Single Institute: Yooju Shin, Sang Yun Ha, Jiyeon Hyeon, Boram Lee, Jeeyun Lee, Kee-Taek Jang, Kyoung-Mee Kim, Young Suk Park, Cheol-Keun Park; Cancer Res Treat. 2015;47(4):738-746. Published online February 16, 2015; DOI: https://doi.org/10.4143/crt.2014.224

Abstract PDF PubReader ePub

Purpose
Management of gastroenteropancreatic (GEP) neuroendocrine tumors with liver metastases (NETLM) presents many clinical challenges. Assessment of the extent of disease and primary tumor site is crucial for management. In this study, we investigated the primary tumor sites and prognostic factors in GEP NETLM among Korean patients. Materials and Methods We reviewed the medical records of 72 Korean patients diagnosed with GEP NETLM between January 1999 and May 2013, focusing on their clinical and pathologic characteristics.
Results
The most frequently encountered primary tumor sites were the pancreas (n=25, 35%), stomach (n=8, 11%), gall bladder (n=4, 6%) and rectum (n=3, 4%). Twenty-five patients (35%) had occult primary tumor. Twelve patients (17%) had histological grade G1 tumors, 30 patients (42%) had G2 tumors, and 30 patients (42%) had G3 tumors. The mean follow-up period after histological confirmation of hepatic metastases was 11.30±2.44 months for G3 tumors, 19.67±4.09 months for G2 tumors, and 30.67±6.51 months for G1 tumors. Multivariate analyses revealed that an unknown primary tumor site (p=0.001) and higher histological grade (p < 0.001) were independent prognostic indicators for shorter overall survival (OS). Most long-term survivors (OS > 24 months) had received antitumor treatment. Conclusion The primary tumor site most frequently associated with GEP NETLM was the pancreas. Unknown primary tumor and higher histological grade were independent prognostic indicators for shorter OS. Patients identified as being at a risk of shorter OS should be followed up closely.

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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 Article

Predictive Value of the ERCC1 Expression for Treatment Response and Survival in Advanced Gastric Cancer Patients Receiving Cisplatin-based First-line Chemotherapy: Jina Yun, Kyoung-Mee Kim, Seung Tae Kim, Jung-Hoon Kim, Jung A Kim, Jee Hyun Kong, Soo Hyeon Lee, Young-Woong Won, Jong-Mu Sun, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2010;42(2):101-106. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.101

Abstract PDF PubReader ePub

Purpose

The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy.

Materials and Methods

A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei.

Results

Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%).

Conclusion

In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.

Citations

Citations to this article as recorded by

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