BACKGROUND AND AIMS: To determine the association between DNA mismatch repair (MMR) protein expression and response to chemotherapy in patients with advanced colorectal cancer (CRC). METHODS: Using immunohistochemistry, tumour expression of 2 MMR genes, hMLH1 and hMSH2, was assessed in 86 patients with advanced CRC, who were treated with either irinotecan alone or in combination with 5-flurouracil/folinic acid. RESULTS: Weak/negative staining in the tumours was associated with the presence of metastases at diagnosis (p = 0.026) and with the time for metastases to appear (p = 0.0001). An objective response to treatment was observed in 32/56 (57%) patients who had tumours with negative/weak MMR protein expression (p = 0.001), compared to 17% of patients with tumours with moderate/strong expression. Those who had tumours with weak/absent expression of either hMLH1 or hMSH2 who received the combination therapy were more likely to show an objective response (p = 0.0001). CONCLUSION: Advanced CRC patients whose tumours have deficient MMR demonstrate a shorter time to metastasis than those with normal hMLH1/hMSH2 expression. Patients with MMR-deficient tumours are also more likely to benefit from combination chemotherapy (irinotecan plus 5-flurouracil/folinic acid).
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Adaptor Proteins, Signal Transducing, Aged, Antineoplastic Combined Chemotherapy Protocols, Base Pair Mismatch, Camptothecin, Colorectal Neoplasms, DNA Repair, Female, Fluorouracil, Gene Expression Regulation, Neoplastic, Humans, Irinotecan, Male, Middle Aged, MutL Protein Homolog 1, MutS Homolog 2 Protein, Neoplasm Metastasis, Nuclear Proteins, Treatment Outcome