Clinicopathologic characteristics and outcomes of gastric cancers with the MSI‐H phenotype

Seo, Hyung Min; Chang, Yeon Soo; Joo, Sun Hyung; Kim, Youn Wha; Park, Yong-Koo; Hong, Sung Wha; Lee, Suk-Hwan

doi:10.1002/jso.21220

Cited by 96 publications

(113 citation statements)

References 26 publications

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“…Several reports, together with our results, have demonstrated that microsatellite-unstable gastric carcinomas are significantly associated with the elderly [2,[4][5][6], women [3,5], and antral location [2,4,5,9]. These characteristics are similar to those of medullary-type, poorly differentiated adenocarcinoma of the colorectum, which is a representative MSI-positive carcinoma showing predominant occurrence in older age, women, and the proximal colon [26].…”

Section: Discussionsupporting

confidence: 78%

“…The present study demonstrates no significant difference in the proportion of MSI between the differentiated type and the undifferentiated type. Although predominant intestinal-type histology in microsatellite-unstable carcinomas has been widely accepted [2,4,5,9,10,23], several reports have shown predominant poorly differentiated histology [1], or no significant association between histological morphology and MSI [6,[11][12][13]. The differences among these reports were considered to depend upon the specific groups of cases studied and the type and number of markers examined.…”

Section: Discussionmentioning

confidence: 99%

“…MSI has been observed in 8-39 % of gastric carcinomas [1][2][3][4][5][6]. Microsatellite-unstable gastric carcinomas have the following clinicopathological features: older age, expanding growth pattern, antral location, intestinal-type histology, a lower incidence of lymph node metastasis, and favorable prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…Predominant intestinal-type histology in microsatelliteunstable gastric carcinomas was widely accepted [2,4,5,9,10]. However, several issues remain poorly defined and are the subject of much debate because of several reports showing predominant poorly differentiated histology [1] or no significant association between histological morphology and MSI [6,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach

et al. 2012

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Background Microsatellite instability (MSI) has been observed in 8-39 % of sporadic gastric cancers. However, despite numerous reports indicating a significant relationship between intestinal-type histology and MSI, detailed correlation between histological subtypes and MSI remains obscure. The purpose of the present study is to clarify the relationship between histological subtype and microsatellite status in gastric carcinomas. Methods Microsatellite status was examined for 464 consecutive gastric carcinomas from 420 patients as well as histological subtypes and other clinicopathological findings.Results MSI was observed in 82 carcinomas (17.7 %), and the greatest proportions were observed in solid-type, poorly differentiated adenocarcinoma (43.0 %) and papillary adenocarcinoma (32.5 %), both being significantly higher than those of other subtypes. The proportion increased with advancing age (0 % at 51-64 years, 8.5 % at 65-74 years, 18.4 % at 75-84 years, 35.3 % at 85-96 years). Compared with microsatellite-stable carcinomas, microsatellite-unstable carcinomas were significantly related with older age, female gender, antral location, and predominant papillary adenocarcinoma and solid-type, poorly differentiated adenocarcinoma. Poorly differentiated type carcinoma was significantly less frequent than differentiated type in microsatellite-unstable cancer at the early stage, whereas no significant difference existed at the advanced stage. Conclusions These results suggest that there are specific histological subtypes with highly frequent MSI and that gastric carcinoma with MSI originates from differentiatedtype carcinomas, indicating histological diversity during tumor growth.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach

et al. 2012

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“…The frequency of microsatelliteinstable gastric adenocarcinoma in our cohort was 16% vs 21.7% in the Cancer Genome Atlas 6 , 22.7% in the Asian Cancer Research Group, 7 and 8-25.9% in the literature. [40][41][42] The reported incidence is higher in western studies 43 and associated with older age, female gender, larger tumor size, intestinal differentiation, and lower rate of nodal involvement. 40,44 In the Asian Cancer Research Group, the microsatellite-instable subtype was predominantly associated with antral location, early stage, and intestinal phenotype as well.…”

Section: Discussionmentioning

confidence: 99%

A protein and mRNA expression-based classification of gastric cancer

et al. 2016

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The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques. Gastric carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Despite better control over known risk factors and development of new chemotherapeutic and targeted agents, in the United States, the 5-year overall survival for gastric cancer patients is only 29%. 1 With regard to patient stratification, although several morphologic classifications have been developed, one broadly used system is the Lauren classification, which divides gastric adenocarcinoma into intestinal and diffuse types. 2 The simple two-tiered classification gives a general understanding of the histogenesis and biology of gastric cancer, and has been particularly helpful in evaluating the epidemiologic data. Another widely used system is the WHO classification, which is based on more precise histologic patterns. It is an all-inclusive system, which recognizes all the rare subtypes that were not identified in the Lauren classification. 3 Nevertheless, its clinical utility is doubtful as there is little difference in outcomes between the distinct histological subgroups.Following the successful Trastuzumab for Gastric Cancer (ToGA) trial, the only validated predictive biomarker for personalized therapy of gastric cancer is limited to human epidermal growth factor receptor (Her2) protein expression. 4 Recently, anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody (ramucirumab) has been FDA approved, and anti-epidermal growth factor receptor (EGFR) an...

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Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer

Połom

Marano

Marrelli

et al. 2017

British Journal of Surgery

213

155

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Clinicopathologic characteristics and outcomes of gastric cancers with the MSI‐H phenotype

Abstract: Gastric cancers with MSI-H have specific clinicopathologic characteristics, such as older age at diagnosis, distal tumor location, increased tumor size, and intestinal histologic type. However, immunohistochemical staining for hMLH1 and hMSH2 is not as accurate as the PCR-based MSI test.

Cited by 96 publications

References 26 publications

Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach

Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach

A protein and mRNA expression-based classification of gastric cancer

Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer

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