Article
Studies on p53, BAX, and Bcl-2 Protein Expression in Stage III (UICC) Colon Cancer Treated by Adjuvant Chemotherapy: Major Prognostic Impact of Proapoptotic BAX Pronounced by Intact p53
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Published: | March 20, 2006 |
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Purpose: To analyze the expression patterns of proapoptotic BAX, antiapoptotic Bcl-2 and p53, the proposed upstream effector of these molecules, as potential prognostic markers in stage III colon cancer treated by adjuvant chemotherapy.
Patients and methods: 188 patients with UICC stage III colon carcinoma who had received a median of 12 cycles of 5-fluorouracil (FU)-based adjuvant chemotherapy (5-FU/folinic acid or 5-FU/levamisole) were enrolled. Median follow-up was 84.5 months. Protein expression patterns of BAX, Bcl-2, and p53 were analyzed by immunohistochemistry on sections of resected tumor samples.
Results: BAX, Bcl-2 and p53 protein expression were high or positive in 59%, 70% and 50% of 188 cases, respectively. BAX was correlated with a higher degree of differentiation (p=0.01), and Bcl-2 was associated with left-sided tumors (p=0.03). In contrast to either p53 or Bcl-2, low BAX, advanced N-category, low grade of differentiation and treatment with 5-FU/levamisole (instead of 5-FU/folinic acid) were univariately associated with poorer disease-free survival (DFS) (p=0.0005, p=0.001, p=0.005, and p=0.01, respectively) and poorer overall survival (OS) (p=0.002, p=0.0001, p=0.003, and p=0.02, respectively). Besides N category and treatment arm, BAX was an independent variable related to both OS and DFS (p=0.003 and p=0.001, respectively). In both univariate and multivariate analysis, the p53 -/BAX high in comparison with the p53 +/BAX high subset confered an significantly improved DFS (p=0.03, respectively) as well as an marginally improved OS (p=0.07 and p=0.08, respectively).
Conclusions: BAX protein expression may be of central significance for clinical outcome to 5-FU-based adjuvant chemotherapy in stage III colon cancer, and bivariate analysis of p53/BAX possibly may provide further prognostic evidence.