Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas

AIMS: The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers. METHODS AND RESULTS: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32). CONCLUSIONS: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.