Objective. To investigate whether defective DNA mismatch repair (MMR) defines a subgroup at risk for recurrence in sporadic endometrial carcinoma patients. Me thods. Primary tumors from 44 patients with recurrent stage I endometrial carcin oma were compared after matching, with tumors of 44 patients being free of recur rence for minimal 3 years. Paraf-fin-embedded primary tumors (n = 88) and recu rrent tumors (n = 32) were subjected to immunohistochemical analysis for hMSH2 a nd hMLH1 expression. Subsequently, a staining index (SI = 0-9) was calculated b ased on staining intensity and quantity. DNA was extracted from paraffin-embedd ed tissues, and promoter methylation of hMLH1 was determined by nested methylati on-specific PCR (MSP). Microsatellite instability (MSI) was assessed by BAT-26 or BAT-25. Results. Low hMSH2 expression was observed in 2%of primary tumors of control patients without recurrence, 14%of primary tumors of patients with r ecurrence, and 0%of recurrent tumors. Low hMLH1 expression was observed in 32% , 19%, and 22%, respectively. hMLH1 gene promoter methylation was detected in 50%, 47%, and 32%, and MSI was found in 16%, 14%, and 30%, respectively. N o significant differences were found between primary tumors of patients with and without recurrence with respect to hMSH2 and hMLH1 expression, hMLH1 promoter m ethylation, and MSI. When primary and recurrent tumors were compared, there was an increased correlation of hMLH1 methylation with low hMLH1 expression and MSI in recurrent tumors. Conclusion. MSI, hMLH1 promoter methylation, and the expres sion of hMLH1 and hMSH2 are not predictive for the development of recurrent stag e I endometrial carcinoma. In the progression of tumor, “de novo”hMLH1 methyla tion rarely occurs, instead there is further derailment of the MMR pathway in af fected tumors.
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