Purpose: Colorectal cancer and gastric cancer are the two most commonly associated malignancies in Japan. We examined mismatch repair deficiency in the tumors of patients with primary colorectal and gastric cancers retrospectively.
Methods: In 103 cases and 102 healthy control subjects, surgical specimens of colorectal and gastric cancer underwent immunohistochemical analysis of mismatch repair proteins (hMLH1 and hMSH2) and microsatellite instability testing.
Results: Immunohistochemical and microsatellite instability testing produced similar results. High microsatellite instability in colorectal cancer was found in 23 of 103 cases (23 percent) with colorectal and gastric cancers, and in 8 of 102 healthy control subjects (8 percent). Twelve (12 percent) had mismatch repair deficiency in both colorectal and gastric cancers, and both tumors had loss of the same mismatch repair protein (hMLH1, n = 5; hMSH2, n = 7). They had the first cancer at a younger age, with a higher frequency of familial colorectal cancer than the others. Seventeen had mismatch repair deficiency in either tumor, which showed loss of expression of hMLH1. Multiple cancers and right-sided colon cancers developed more frequently in patients with mismatch repair deficiency.
Conclusions: Patients with both colorectal and gastric cancers are more likely to have phenotypic evidence of hereditary nonpolyposis colorectal cancer than patients with colorectal cancer only. Among patients with double tumors, 12 percent showed a common deficiency in the same mismatch repair protein in both tumors by immunohistochemistry, and they should undergo genetic counseling for germline mutational analysis. Immunohistochemistry was effective in detecting mismatch repair deficiency of colorectal and gastric cancer as well as microsatellite instability testing, and may be more practical to perform phenotypic analysis of tumors because of its cost-effectiveness.