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

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129 Scopus citations

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
DOIs
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Halling, K. C., Harper, J., Moskaluk, C. A., Thibodeau, S. N., Petroni, G. R., Yustein, A. S., Tosi, P., Minacci, C., Roviello, F., Piva, P., Hamilton, S. R., Jackson, C. E., & Powell, S. M. (1999). Origin of microsatellite instability in gastric cancer. American Journal of Pathology, 155(1), 205-211. https://doi.org/10.1016/S0002-9440(10)65114-0