Deficiency of hMLH1 and hMSH2 Expression Is a Poor Prognostic Factor in Esophageal Squamous Cell Carcinoma

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Background:The human Mut-L-Homologon-1 (MLH1) and Mut-S-Homologon-2 (MSH2) are post replication mismatch repair (MMR) genes.Methods:We examined the correlation of the clinical features of 122 patients with esophageal squamous cell carcinoma (ESCC) with the expression of MLH1 and MSH2 by immunohistochemical analysis.Results:According to our criteria, 34 and 25 cases did not express MLH1 and MSH2, respectively. Expression of both the MLH1 and MSH2 gene products was observed in 73 (59.8%) cases; loss of MLH1 or MSH2 expression was detected in 35(28.7%) cases. Fourteen (11.5%) cases demonstrated loss of both MLH1 and MSH2 expression in ESCC. Loss of MLH1 and/or MSH2 gene expression significantly correlated with increases in malignancy, as evidenced by increases in the existence of metastatic lymph nodes (P = 0.0056), extensive invasion (P = 0.0007), and poor differentiation (P = 0.0992). The MLH1-negative patients had a significantly poorer prognosis than those in the MLH1-positive group (P = 0.0043). Similar results were observed for MSH2 expression (P = 0.0002). Patients both MLH1 and MSH2 negative exhibited the most poor clinical outcome than other patients (P < 0.0001).Conclusion:We conclude that MMR protein expression, detected by immunohistochemistry, is a useful marker providing information necessary to decide appropriate therapeutic strategies in patients with ESCC.

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