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.
UNLABELLED: This study in 716 colon cancerpatients 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 cancerpatients 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: Florencia McAllister; Danielle M Pineda; Masaya Jimbo; Shruti Lal; Richard A Burkhart; Jennifer Moughan; Kathryn A Winter; Kotb Abdelmohsen; Myriam Gorospe; Ana de Jesus Acosta; Rachana H Lankapalli; Jordan M Winter; Charles J Yeo; Agnieska K Witkiewicz; Christine A Iacobuzio-Donahue; Daniel Laheru; Jonathan R Brody Journal: Cancer Biol Ther Date: 2014-03-11 Impact factor: 4.742
Authors: Artur Mezheyeuski; Ina Hrynchyk; Mia Karlberg; Anna Portyanko; Lars Egevad; Peter Ragnhammar; David Edler; Bengt Glimelius; Arne Östman Journal: Sci Rep Date: 2016-11-02 Impact factor: 4.379