Distinct clinical features and outcomes of gastric cancers with microsatellite instability

Hye Seung Lee; Seung Im Choi; Hyeon Kook Lee; Hee Sung Kim; Han Kwang Yang; Gyeong Hoon Kang; Yong I. Il Kim; Byung Lan Lee; Woo Ho Kim

doi:10.1038/modpathol.3880578

Distinct clinical features and outcomes of gastric cancers with microsatellite instability

Hye Seung Lee, Seung Im Choi, Hyeon Kook Lee, Hee Sung Kim, Han Kwang Yang, Gyeong Hoon Kang, Yong I. Il Kim, Byung Lan Lee, Woo Ho Kim

Department of Surgery

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

Abstract

Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <. 05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <. 001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-β type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =. 046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.

Original language	English
Pages (from-to)	632-640
Number of pages	9
Journal	Modern Pathology
Volume	15
Issue number	6
DOIs	https://doi.org/10.1038/modpathol.3880578
State	Published - 2002

Bibliographical note

Funding Information:
Copyright © 2002 by The United States and Canadian Academy of Pathology, Inc. VOL. 15, NO. 6, P. 632, 2002 Printed in the U.S.A. Date of acceptance: March 12, 2002. This study was supported by the 21C Frontier Functional Human Genome Project of the Ministry of Science and Technology of Korea. Address reprint requests to: Woo Ho Kim, M.D., Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea; e-mail: [email protected]; fax: 82-2-765-5600.

Keywords

Gastric cancer
Microstellite instability
Survival analysis

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10.1038/modpathol.3880578

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title = "Distinct clinical features and outcomes of gastric cancers with microsatellite instability",

abstract = "Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <. 05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <. 001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-β type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =. 046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.",

keywords = "Gastric cancer, Microstellite instability, Survival analysis",

author = "Lee, {Hye Seung} and Choi, {Seung Im} and Lee, {Hyeon Kook} and Kim, {Hee Sung} and Yang, {Han Kwang} and Kang, {Gyeong Hoon} and {Il Kim}, {Yong I.} and Lee, {Byung Lan} and Kim, {Woo Ho}",

note = "Funding Information: Copyright {\textcopyright} 2002 by The United States and Canadian Academy of Pathology, Inc. VOL. 15, NO. 6, P. 632, 2002 Printed in the U.S.A. Date of acceptance: March 12, 2002. This study was supported by the 21C Frontier Functional Human Genome Project of the Ministry of Science and Technology of Korea. Address reprint requests to: Woo Ho Kim, M.D., Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea; e-mail: [email protected]; fax: 82-2-765-5600.",

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doi = "10.1038/modpathol.3880578",

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AU - Choi, Seung Im

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AU - Kim, Hee Sung

AU - Yang, Han Kwang

AU - Kang, Gyeong Hoon

AU - Il Kim, Yong I.

AU - Lee, Byung Lan

AU - Kim, Woo Ho

N1 - Funding Information: Copyright © 2002 by The United States and Canadian Academy of Pathology, Inc. VOL. 15, NO. 6, P. 632, 2002 Printed in the U.S.A. Date of acceptance: March 12, 2002. This study was supported by the 21C Frontier Functional Human Genome Project of the Ministry of Science and Technology of Korea. Address reprint requests to: Woo Ho Kim, M.D., Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea; e-mail: [email protected]; fax: 82-2-765-5600.

PY - 2002

Y1 - 2002

N2 - Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <. 05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <. 001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-β type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =. 046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.

AB - Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <. 05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <. 001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-β type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =. 046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.

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Distinct clinical features and outcomes of gastric cancers with microsatellite instability

Abstract

Bibliographical note

Keywords

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