title: A combined analysis of mismatch repair status and thymidylate synthase expression in stage II and III colon cancer.
abstract: This study in 716 colon cancer patients evaluates if a combined instead of a single marker analysis of mismatch repair (MMR) status and thymidylate synthase (TS) expression could individualize the treatment decision. The results indicate that a combined analysis of MMR status and TS expression can improve prediction of response to adjuvant 5-fluorouracil (5-FU)-based chemotherapy in stage III colon cancer.
  
  
  BACKGROUND
  Colon cancer with mismatch repair deficiency and low TS expression has been associated with an improved prognosis. Data also indicate that MMR proficient colon cancer with high TS expression has a better response to adjuvant 5-FU-based chemotherapy. This study evaluates if a combined analysis of MMR status and TS expression in colon cancer can add prognostic value and better predict response to adjuvant 5-FU-based chemotherapy. The potential relationship between MMR status and TS expression is also investigated.
  
  
  METHODS
  This study includes a subgroup of 716 patients with colon cancer out of 2224 stage II and stage III colorectal cancer patients enrolled in Nordic trials randomized to surgery alone or surgery plus adjuvant 5-FU-based chemotherapy. After immunohistochemical analysis of tumor MMR status and TS expression the patients were divided into 4 groups.
  
  
  RESULTS
  There was a nonsignificant difference in overall survival between group 1 (patients with deficient MMR tumors with low TS) and group 4 (patients with proficient MMR tumors expressing high TS). When comparing group 1 and group 4 patients treated with surgery alone a trend to better overall survival was found in group 1, P=.06. In group 4, stage III patients had a significantly improved survival when receiving adjuvant 5-FU-based chemotherapy compared with surgery alone, P=.01. No relationship was found between MMR status and TS expression.
  
  
  CONCLUSIONS
  A combined instead of a single marker analysis of MMR status and TS expression can improve the prediction of response to 5-FU-based chemotherapy in stage III colon cancer.
authors.affiliation: Karolinska Institutet, Department of Oncology-Pathology, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Öhrling
authors.forename: Mia
authors.initials: M
authors.lastname: Karlberg
authors.forename: David
authors.initials: D
authors.lastname: Edler
authors.forename: Marja
authors.initials: M
authors.lastname: Hallström
authors.forename: Peter
authors.initials: P
authors.lastname: Ragnhammar
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D053843:DNA Mismatch Repair; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D013940:Thymidylate Synthase; D005472:Fluorouracil