title: Mismatch repair status is a predictive factor of tumour response to 5-fluorouracil and irinotecan chemotherapy in patients with advanced colorectal cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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).
authors: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. riyben@utu.fi
authors: R
authors: R
authors: Bendardaf
authors: H
authors: H
authors: Lamlum
authors: R
authors: R
authors: Ristamäki
authors: E
authors: E
authors: Korkeila
authors: K
authors: K
authors: Syrjänen
authors: S
authors: S
authors: Pyrhönen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020137:Base Pair Mismatch; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004260:DNA Repair; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000096:biosynthesis; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000077146:Irinotecan; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D005472:Fluorouracil; D002166:Camptothecin