Overexpression of p53 protein and outcome of patients treated with chemoradiation for carcinoma of the anal canal - A report of randomized trial RTOG87-04

BAGKGROUND. Despite encouraging results with chemoradiation as the primary means of managing carcinoma of the anal canal, approximately 20% of patient s will develop a local recurrence. This study examined the prognostic signi ficance of p53 nuclear protein overexpression in the pretreatment biopsies of patients treated with chemoradiation for epidermoid carcinoma of the ana l canal. METHODS. All patients were treated in a prospective, randomized Radiation T herapy Oncology Group trial (RTOG 87-04) in which radiotherapy to the pelvi s was compared with, concurrent 5-fluorouracil (5-FU) or 5-FU and mitomycin -C. Formalin fixed, paraffin embedded blocks or unstained slides from the p retreatment biopsies of 64 patients were obtained from referring institutio ns and evaluated immunohistochemically with the polyclonal p53 antibody CM- 1. A multivariate analysis was conducted to analyze overexpression of p53 i n terms of locoregional control, no evidence of disease (NED), and overall survival. RESULTS. p53 protein was overexpressed in 48.4% of the cases. Although not statistically significant, there was a trend for patients whose rumors over expressed p53 to have inferior locoregional control (52% vs. 72%, P = 0.13) , NED survival (52% vs; 68%, P = 0.27), and absolute survival (58% vs. 78%, P = 0.14). Of all the pretreatment factors analyzed, only International Un ion Against Cancer stage was predictive of outcome in multivariate analysis . Among those patients whose tumors overexpressed p53, there was a trend to ward improved outcome in the arm that received 5-FU and mitomycin-C compare d with the arm that received 5-FU only. CONCLUSIONS. Overexpression of the p53 protein may be associated with infer ior outcome for patients managed with definitive chemoradiation for epiderm oid carcinoma of the anal canal. Cancer 1999;85:126-33. (C) 1999 American C ancer Society.