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

ABSTRACT

OBJECTIVES: We examined the correlation between microsatellite instability (MSI) status and the clinicopathological features and prognostic value in gastric cancer and compared the efficacy of immunohistochemical staining for hMLH1 and hMSH2 with a polymerase chain reaction (PCR)-based test. METHODS: MSI status was examined in 328 consecutive gastric adenocarcinomas using tissue preserved in paraffin blocks. DNA extracted from tumor sections and the corresponding normal tissue was analyzed using PCR at the five microsatellite loci recommended by the National Cancer Institute (NCI). Immunohistochemical staining for hMLH1 and hMSH2 was performed and the results were compared with the MSI status measured using PCR. The relationship of the clinicopathologic variables to MSI status was analyzed. RESULTS: Of the gastric cancers, 8.2% (n = 27) contained MSI-H and this was associated with older age (>70 years), distal tumor location, tumor size, and intestinal subtype. Lymphatic and vascular invasion were associated with the disease-free survival. On immunohistochemical staining, the loss of expression of hMLH1 or hMSH2 was observed in 11% (n = 36). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of immunohistochemical staining were 63.0%, 93.7%, 47.2%, 96.6%, and 91.2%, respectively. CONCLUSIONS: 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.