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  • Title: A combined analysis of mismatch repair status and thymidylate synthase expression in stage II and III colon cancer.
    Author: Öhrling K, Karlberg M, Edler D, Hallström M, Ragnhammar P.
    Journal: Clin Colorectal Cancer; 2013 Jun; 12(2):128-35. PubMed ID: 23276521.
    Abstract:
    UNLABELLED: 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. PATIENTS AND 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.
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