Mismatch repair status is a predictive factor of tumour response to 5-fluorouracil and irinotecan chemotherapy in patients with advanced colorectal cancer

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).