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Tumour Biol. 2007;28(4):212-20. Epub 2007 Aug 24.

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

Author information

1
Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. riyben@utu.fi

Abstract

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).

PMID:
17717427
DOI:
10.1159/000107417
[Indexed for MEDLINE]

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