P27 Kip1 in stage III colon cancer: Implications for outcome following adjuvant chemotherapy in cancer and leukemia group B protocol 89803

Monica M. Bertagnolli, Robert S.Warren, Donna Niedzwiecki, Elke Mueller, Carolyn C. Compton, Mark Redston, Margaret Hall, Hejin P. Hahn, Scott D. Jewell, Robert J. Mayer, Richard M. Goldberg, Leonard B. Saltz, Massimo Loda

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: In retrospective studies, loss of p27 Kip1 (p27), a cyclin-dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for stage III colon cancer. Methods: Cancer and Leukemia Group B protocol 89803 randomized 1,264 stage III colon cancer patients to receive weekly bolus 5-fluorouracil/leucovorin or weekly bolus irinotecan, 5-fluo-rouracil, and leucovorin (lFL). The primary end point was overall survival (OS); disease-free survival was a secondary endpoint. Expression of p27 and DNA mismatch repair proteins were determined by immunohistochemistry in primary tumor and normal tissue from paraffin blocks. Data were analyzed using log-rank test. Results: Of 601 tumors analyzed, 207 (34.4%) showed p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27-negative tumors showed reduced OS [5-year OS 66%: 95% confidence interval (95% CI), 0.59-0.72 versus 75%: 95% CI, 0.70-0.79; log-rank P = 0.021]. This relationship was not influenced by treatment arm. Combination of p27 status with mismatch repair status, however, identified a small subset of patients that may benefit from lFL (n = 36; 5-year disease-free survival 81%: 95% CI, 0.64-0.98 versus 47%: 95% CI, 0.21-0.72; log-rank P = 0.042; 5-year OS 81%: 95% CI, 0.64-0.98 versus 60%: 95% CI, 0.35-0.85; log-rank P = 0.128). Conclusions: Loss of p27 is associated with reduced survival in stage III colon cancer but by itself does not indicate a significant difference in outcome between patients treated lFL or 5-fluorouracil/leucovorin.

Original languageEnglish (US)
Pages (from-to)2116-2122
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
StatePublished - Mar 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Bertagnolli, M. M., S.Warren, R., Niedzwiecki, D., Mueller, E., Compton, C. C., Redston, M., Hall, M., Hahn, H. P., Jewell, S. D., Mayer, R. J., Goldberg, R. M., Saltz, L. B., & Loda, M. (2009). P27 Kip1 in stage III colon cancer: Implications for outcome following adjuvant chemotherapy in cancer and leukemia group B protocol 89803. Clinical Cancer Research, 15(6), 2116-2122. https://doi.org/10.1158/1078-0432.CCR-08-2674