P53 STATUS IN COLORECTAL CANCER

Clin Cancer Res. 2013 Aug 27. [Epub ahead of print]

Association of TP53 Mutational Status and Gender with Survival After Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803.

Warren RS, Atreya CE, Niedzwiecki D, Weinberg V, Donner DB, Mayer RJ, Goldberg RM, Compton C, Zuraek MB, Ye X, Saltz LB, Bertagnolli MM.

Source

Surgery and the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco.

Abstract

PURPOSE:

The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA binding domain of TP53 are associated with survival in stage III colon cancer.

EXPERIMENTAL DESIGN:

The impact of TP53 genotype was prospectively evaluated in CALGB 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan.

RESULTS:

TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease free survival or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type vs. zinc binding or non-zinc binding mutations in the TP53 DNA binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc-binding, or non zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men.

CONCLUSIONS:

The presence of any TP53 mutation within the DNA binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.