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Clinical significance of microsatellite instability for stage II or III colorectal cancer following adjuvant therapy with doxifluridine

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Abstract

Microsatellite instability (MSI) is a molecular marker that can provide valuable prognostic information for colorectal cancer (CRC). However, the predictive role of the MSI status remains less clear than its role in prognostication due to mixed results from previous studies. Therefore, this study investigated the usefulness of the MSI status as a predictive factor for stage II or III CRC patients who received adjuvant doxifluridine therapy. Among 3030 patients with CRC who underwent surgical resection between 1997 and 2006, 564 patients were diagnosed with stage II or III, and adjuvant doxifluridine therapy was administered to 394 patients (70.0%). The MSI status was assessed using the markers BAT25 and BAT26, and samples with instability at both markers were scored as exhibiting high-frequency MSI (MSI-H). Among the 564 patients, 290 patients (51.4%) had stage II, and MSI-H was found in 41 patients (7.3%). With a median follow-up duration of 35.1 months (range, 0.5–135.2), the 5-year overall survival (OS) rate and relapse-free survival (RFS) rate were 87.5 and 76.2%, respectively. MSI-H showed a favorable survival trend for OS (P = 0.098) and significant survival benefit for RFS (P = 0.037) in all patients. In a univariate analysis, the doxifluridine-treated patients with MSI-H showed improved RFS compared to those with low or stable MSI (MSI-L/S) (P = 0.036), while the MSI status was not significantly associated with OS (P = 0.107). In a multivariate analysis, MSI-H was not significantly associated with RFS (Hazard ratio = 2.467, P = 0.125). In conclusion, this study confirmed the positive prognostic role of MSI-H. However, MSI-H patients with stage II or III CRC did not seem to benefit from doxifluridine adjuvant therapy.

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References

  1. Sinicrope FA, Sargent DJ. Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol. 2009;21:369–73.

    Article  PubMed  CAS  Google Scholar 

  2. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.

    PubMed  CAS  Google Scholar 

  3. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69–77.

    Article  PubMed  CAS  Google Scholar 

  4. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–18.

    Article  PubMed  CAS  Google Scholar 

  5. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.

    Article  PubMed  CAS  Google Scholar 

  6. Samowitz WS, Curtin K, Ma KN, Schaffer D, Coleman LW, Leppert M, et al. Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev. 2001;10:917–23.

    PubMed  CAS  Google Scholar 

  7. Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375:1030–47.

    Article  PubMed  Google Scholar 

  8. Des Guetz G, Uzzan B, Nicolas P, Schischmanoff O, Perret GY, Morere JF. Microsatellite instability does not predict the efficacy of chemotherapy in metastatic colorectal cancer. A systematic review and meta-analysis. Anticancer Res. 2009;29:1615–20.

    PubMed  CAS  Google Scholar 

  9. Jover R, Zapater P, Castells A, Llor X, Andreu M, Cubiella J, et al. The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status. Eur J Cancer. 2009;45:365–73.

    Article  PubMed  CAS  Google Scholar 

  10. Bertagnolli MM, Niedzwiecki D, Compton CC, Hahn HP, Hall M, Damas B, et al. Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol. 2009;27:1814–21.

    Article  PubMed  CAS  Google Scholar 

  11. Jensen LH, Danenberg KD, Danenberg PV, Jakobsen A. Predictive value of MSH2 gene expression in colorectal cancer treated with capecitabine. Clin Colorectal Cancer. 2007;6:433–5.

    Article  PubMed  CAS  Google Scholar 

  12. Niitani H, Kimura K, Saito T, Nakao I, Abe O, Urushizaki I, et al. Phase II study of 5′-deoxy-5-fluorouridine (5′-DFUR) in patients with malignant cancer–a multi-institutional cooperative study. Gan To Kagaku Ryoho. 1985;12:2044–51.

    PubMed  CAS  Google Scholar 

  13. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998;34:1274–81.

    Article  PubMed  CAS  Google Scholar 

  14. Jo WS, Carethers JM. Chemotherapeutic implications in microsatellite unstable colorectal cancer. Cancer Biomark. 2006;2:51–60.

    PubMed  CAS  Google Scholar 

  15. Bellizzi AM, Frankel WL. Colorectal cancer due to deficiency in DNA mismatch repair function: a review. Adv Anat Pathol. 2009;16:405–17.

    Article  PubMed  CAS  Google Scholar 

  16. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28:3219–26.

    Article  PubMed  CAS  Google Scholar 

  17. Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B. Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet. 2000;355:1745–50.

    Article  PubMed  CAS  Google Scholar 

  18. Kim GP, Colangelo LH, Wieand HS, Paik S, Kirsch IR, Wolmark N, et al. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol. 2007;25:767–72.

    Article  PubMed  CAS  Google Scholar 

  19. Lamberti C, Lundin S, Bogdanow M, Pagenstecher C, Friedrichs N, Buttner R, et al. Microsatellite instability did not predict individual survival of unselected patients with colorectal cancer. Int J Colorectal Dis. 2007;22:145–52.

    Article  PubMed  CAS  Google Scholar 

  20. Kim ST, Lee J, Park SH, Park JO, Lim HY, Kang WK, et al. Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy. Cancer Chemother Pharmacol. 2010;66(4):659–67.

    Article  PubMed  CAS  Google Scholar 

  21. Yamada Y. Current status of chemotherapy for advanced colorectal cancer in Japan. Clin Colorectal Cancer. 2008;7:15–24.

    Article  PubMed  CAS  Google Scholar 

  22. Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I, Kerr D. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 2009;9:489–99.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 200 Dongduk-Ro, Daegu, Jung-Gu, 700-712, South Korea

    Byung Woog Kang, Jong Gwang Kim, Soo Jung Lee, Yee Soo Chae, Joon Ho Moon & Sang Kyun Sohn

  2. Department of Gastroenterology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 200 Dongduk-Ro, Daegu, Jung-Gu, 700-712, South Korea

    Seong Woo Jeon & Min Kyu Jung

  3. Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 200 Dongduk-Ro, Daegu, Jung-Gu, 700-712, South Korea

    Kyoung-Hoon Lim, You Seok Jang, Jun Seok Park, Soo Han Jun & Gyu-Seog Choi

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  1. Byung Woog Kang
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  2. Jong Gwang Kim
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  3. Soo Jung Lee
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Correspondence to Jong Gwang Kim or Gyu-Seog Choi.

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Jong Gwang Kim and Gyu-Seog Choi are contributed equally to this work.

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Kang, B.W., Kim, J.G., Lee, S.J. et al. Clinical significance of microsatellite instability for stage II or III colorectal cancer following adjuvant therapy with doxifluridine. Med Oncol 28 (Suppl 1), 214–218 (2011). https://doi.org/10.1007/s12032-010-9701-2

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  • DOI: https://doi.org/10.1007/s12032-010-9701-2

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