Clinicopathologic implications of hMSH2 gene expression and microsatellite instability in prostate cancer.

Human mismatch repair (MMR) genes encode highly conserved interacting proteins that correct replication errors predisposing to hereditary gastrointestinal and genitourinary malignancies. We previously investigated expression of the prototype MMR gene hMSH2 in normal, benign prostatic hyperplasia and malignant prostate tissues (Velasco et al., Cancer 94:690-699, 2002). An association was detected between reduced hMSH2 staining and favorable outcome as determined by undetectable serum prostate specific antigen (PSA) after radical prostatectomy. We now investigate the association between clinicopathological variables and hMSH2 expression or microsatellite instability (MSI). A statistically significant association was found between tumors exhibiting MSI (MSI+ tumors) and lower preoperative serum PSA values, smaller tumor volumes and lower frequency of surgical specimens with extracapsular extension of tumor. No statistically significant association (P value less than or equal to 0.05) was found between hMSH2 staining and these clinicopathologic variables. Based on our analysis, we conclude that MMR deficiency has important clinicopathologic implications in prostate cancer. Furthermore, specific MMR genes may have different effects on prostate cancer biology.