Origin of microsatellite instability in gastric cancer

Kevin C. Halling, Jeffrey Harper, Christopher A. Moskaluk, Stephen N Thibodeau, Gina R. Petroni, Aron S. Yustein, Piero Tosi, Chiara Minacci, Franco Roviello, Paolo Piva, Stanley R. Hamilton, Charles E. Jackson, Steven M. Powell

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Microsatellite instability (MSI) is observed in 13-44% of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer, expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16%) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17% of loci, whereas the remaining 10 exhibited high-rate MSI (MSI-H) with instability at > 33% of loci examined. Immunohistochemical staining for hMLH1 and hMSH2 was performed on eight of the tumors with MSI-H, five with MSI-L, and 15 tumors without MSI. All eight tumors with MSI-H showed loss of staining for either hMLH1 (n = 5) or hMSH2 (n = 3). In contrast, tumors with MSI-L or without MSI all showed normal hMSH2 and hMLH1 protein expression patterns. Moreover, all eight of the tumors with MSI-H also showed instability at BAT-26, whereas none of the MSI- L tumors or tumors without instability showed instability at BAT-26. These findings suggest that the majority of high-level MSI in gastric cancer is associated with defects of the mismatch repair pathway. Although larger studies are needed, BAT-26 appears to be a sensitive and specific marker for the MSI-H phenotype in gastric carcinoma.

Original languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalAmerican Journal of Pathology
Volume155
Issue number1
StatePublished - 1999

Fingerprint

Microsatellite Instability
Stomach Neoplasms
Neoplasms
Stomach
Carcinoma
DNA Mismatch Repair
Staining and Labeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Halling, K. C., Harper, J., Moskaluk, C. A., Thibodeau, S. N., Petroni, G. R., Yustein, A. S., ... Powell, S. M. (1999). Origin of microsatellite instability in gastric cancer. American Journal of Pathology, 155(1), 205-211.

Origin of microsatellite instability in gastric cancer. / Halling, Kevin C.; Harper, Jeffrey; Moskaluk, Christopher A.; Thibodeau, Stephen N; Petroni, Gina R.; Yustein, Aron S.; Tosi, Piero; Minacci, Chiara; Roviello, Franco; Piva, Paolo; Hamilton, Stanley R.; Jackson, Charles E.; Powell, Steven M.

In: American Journal of Pathology, Vol. 155, No. 1, 1999, p. 205-211.

Research output: Contribution to journalArticle

Halling, KC, Harper, J, Moskaluk, CA, Thibodeau, SN, Petroni, GR, Yustein, AS, Tosi, P, Minacci, C, Roviello, F, Piva, P, Hamilton, SR, Jackson, CE & Powell, SM 1999, 'Origin of microsatellite instability in gastric cancer', American Journal of Pathology, vol. 155, no. 1, pp. 205-211.
Halling KC, Harper J, Moskaluk CA, Thibodeau SN, Petroni GR, Yustein AS et al. Origin of microsatellite instability in gastric cancer. American Journal of Pathology. 1999;155(1):205-211.
Halling, Kevin C. ; Harper, Jeffrey ; Moskaluk, Christopher A. ; Thibodeau, Stephen N ; Petroni, Gina R. ; Yustein, Aron S. ; Tosi, Piero ; Minacci, Chiara ; Roviello, Franco ; Piva, Paolo ; Hamilton, Stanley R. ; Jackson, Charles E. ; Powell, Steven M. / Origin of microsatellite instability in gastric cancer. In: American Journal of Pathology. 1999 ; Vol. 155, No. 1. pp. 205-211.
@article{21ef4e44267f40918af7caa0cdefdb81,
title = "Origin of microsatellite instability in gastric cancer",
abstract = "Microsatellite instability (MSI) is observed in 13-44{\%} of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer, expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16{\%}) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17{\%} of loci, whereas the remaining 10 exhibited high-rate MSI (MSI-H) with instability at > 33{\%} of loci examined. Immunohistochemical staining for hMLH1 and hMSH2 was performed on eight of the tumors with MSI-H, five with MSI-L, and 15 tumors without MSI. All eight tumors with MSI-H showed loss of staining for either hMLH1 (n = 5) or hMSH2 (n = 3). In contrast, tumors with MSI-L or without MSI all showed normal hMSH2 and hMLH1 protein expression patterns. Moreover, all eight of the tumors with MSI-H also showed instability at BAT-26, whereas none of the MSI- L tumors or tumors without instability showed instability at BAT-26. These findings suggest that the majority of high-level MSI in gastric cancer is associated with defects of the mismatch repair pathway. Although larger studies are needed, BAT-26 appears to be a sensitive and specific marker for the MSI-H phenotype in gastric carcinoma.",
author = "Halling, {Kevin C.} and Jeffrey Harper and Moskaluk, {Christopher A.} and Thibodeau, {Stephen N} and Petroni, {Gina R.} and Yustein, {Aron S.} and Piero Tosi and Chiara Minacci and Franco Roviello and Paolo Piva and Hamilton, {Stanley R.} and Jackson, {Charles E.} and Powell, {Steven M.}",
year = "1999",
language = "English (US)",
volume = "155",
pages = "205--211",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Origin of microsatellite instability in gastric cancer

AU - Halling, Kevin C.

AU - Harper, Jeffrey

AU - Moskaluk, Christopher A.

AU - Thibodeau, Stephen N

AU - Petroni, Gina R.

AU - Yustein, Aron S.

AU - Tosi, Piero

AU - Minacci, Chiara

AU - Roviello, Franco

AU - Piva, Paolo

AU - Hamilton, Stanley R.

AU - Jackson, Charles E.

AU - Powell, Steven M.

PY - 1999

Y1 - 1999

N2 - Microsatellite instability (MSI) is observed in 13-44% of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer, expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16%) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17% of loci, whereas the remaining 10 exhibited high-rate MSI (MSI-H) with instability at > 33% of loci examined. Immunohistochemical staining for hMLH1 and hMSH2 was performed on eight of the tumors with MSI-H, five with MSI-L, and 15 tumors without MSI. All eight tumors with MSI-H showed loss of staining for either hMLH1 (n = 5) or hMSH2 (n = 3). In contrast, tumors with MSI-L or without MSI all showed normal hMSH2 and hMLH1 protein expression patterns. Moreover, all eight of the tumors with MSI-H also showed instability at BAT-26, whereas none of the MSI- L tumors or tumors without instability showed instability at BAT-26. These findings suggest that the majority of high-level MSI in gastric cancer is associated with defects of the mismatch repair pathway. Although larger studies are needed, BAT-26 appears to be a sensitive and specific marker for the MSI-H phenotype in gastric carcinoma.

AB - Microsatellite instability (MSI) is observed in 13-44% of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer, expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16%) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17% of loci, whereas the remaining 10 exhibited high-rate MSI (MSI-H) with instability at > 33% of loci examined. Immunohistochemical staining for hMLH1 and hMSH2 was performed on eight of the tumors with MSI-H, five with MSI-L, and 15 tumors without MSI. All eight tumors with MSI-H showed loss of staining for either hMLH1 (n = 5) or hMSH2 (n = 3). In contrast, tumors with MSI-L or without MSI all showed normal hMSH2 and hMLH1 protein expression patterns. Moreover, all eight of the tumors with MSI-H also showed instability at BAT-26, whereas none of the MSI- L tumors or tumors without instability showed instability at BAT-26. These findings suggest that the majority of high-level MSI in gastric cancer is associated with defects of the mismatch repair pathway. Although larger studies are needed, BAT-26 appears to be a sensitive and specific marker for the MSI-H phenotype in gastric carcinoma.

UR - http://www.scopus.com/inward/record.url?scp=0032984373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032984373&partnerID=8YFLogxK

M3 - Article

C2 - 10393852

AN - SCOPUS:0032984373

VL - 155

SP - 205

EP - 211

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -