Histopathology and mismatch repair status of 458 consecutive colorectal carcinomas.

Defects in the mismatch repair (MMR) genes hMLH1 and hMSH2 have been found in 10% to 20% of sporadic colorectal carcinomas and also many cases of hereditary nonpolyposis colorectal cancer syndrome. Patients with these tumors have an improved prognosis and may show greater sensitivity to chemotherapy. We examined 458 resected colorectal carcinomas from 430 consecutive patients and used immunohistochemistry to determine which tumors lacked expression of these genes (MMR-d). We correlated the status of MMR-d or "intact" expression with stage, site, and histology. Eighty-nine of 458 tumors (19.4%) were MMR-d, including 80 hMLH1 and 9 hMSH2 tumors. A total of 6% of patients had synchronous tumors, and 37.7% of these were MMR-d (P=0.0008). A high proportion of patients with previous breast cancer (4 of 6 patients) had hMLH1-defective colorectal carcinomas. MMR-d tumors presented at an earlier stage than intact tumors, and the node-positive MMR-d tumors were less likely than intact tumors to have pericolonic extranodal tumor deposits (18.2% vs. 44%). The proportion of tumors at each site that were MMR-d increased progressively from cecum (32%) to ascending (35%) to transverse colon, where 41% of all tumors were defective. The proportions then rapidly decreased, reaching the lowest rate (4.7%) in the rectum. Both types of MMR-d tumors more often had expansive borders, intraepithelial lymphocytosis, peritumoral lymphoid, and Crohn's-like lymphoid responses than the intact tumors; the frequencies of these features diminished with advancing stage. Tumor budding was less common in stage II and III MMR-d tumors than in intact tumors. Keloid and myxoid type stromas correlated with stage and vascular invasion and were not related to mismatch repair status. Significant differences existed between the hMLH1 and hMSH2 tumors. The reported right-sided preponderance of MMR-d tumors is due to most hMLH1, but not hMSH2, tumors being found there (87.5% vs. 44.4%). hMSH2 tumors were most common in the rectum (55.6%). Mucinous tumors were common in hMLH1 tumors (36.3%) but not in hMSH2 tumors (11.1%). hMLH1 tumors were most likely to be poorly differentiated (70%), which was uncommon with hMSH2 tumors (22.2%). hMSH2 tumors were more likely to be confined to the wall (66.7%) than hMLH1 (20%) or intact tumors (23%). We conclude that hMLH1 and hMSH2-defective tumors have distinctly differing histologic features from each other.