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From the Department of Laboratory Medicine and
Pathology,*
Mayo Clinic and Foundation, Rochester,
Minnesota; Department of Medicine,
Department
of Pathology,
Division of Biostatistics and
Epidemiology,§
University of Virginia Health
Sciences Center, Charlottesville, Virginia; Divisione di
Chirurgia,¶
Ospedale di Stato, Gorgo Maggiore, Republic of San
Marino; Istituto di Anatomia Eistologia Patologica,||
and
Istituto Policattedva di Scienze
Chirurgiche,
Università Degli Studi
di Siena, Siena, Italy; Division of Pathology and Laboratory
Medicine,**
University of Texas, MD Anderson Cancer Center,
Houston, Texas and Department of
Medicine,
Henry Ford Hospital,
Detroit, Michigan
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.
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