Prognostic role of p53 protein expression in epidermoid carcinoma of the anal canal

Purpose: To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by ra diation therapy (XRT), 5-fluorouracil (5-FU), and mitomycin C (MMC). Methods and Materials: From January 1991 to December 1993, 58 consecutive p atients with primary epidermoid carcinoma of the anal canal were treated in a prospectively designed protocol of XRT (24 Gy/12-3 1/2 wk split-28 Gy/14 ) and concurrent 5-FU (1000 mg/m(2)/day 1-4) and MMC (10 mg/m(2) day 1) of each cycle of XRT. Paraffin-embedded tumor samples were unavailable in 9 pa tients, leaving 49 patients in the study. Expression of p53 protein was stu died using immunohistochemistry and quantified as percent tumor nuclei show ing positive staining. Actuarial survival and disease-free survival (DFS) r ates were estimated by the Kaplan-Meier method, and compared using the log- rank test. A Cox proportional hazard model was used for the multivariable a nalysis. Results: There were 6 T1, 26 T2, 7 T3, and 10 T4 lesions. Primary tumor siz es ranged from 1-15 cm with a median of 4 cm. There were 6 patients with no dal metastases. Median follow-up was 4.5 years. Positive nuclear immunostai ning for p53 was observed in 40 of 49 patients. The median percent positive staining was 5%, with 13, 9, and 18 patients showing staining in <5%, 5 to <10%, and 10-50% of tumor nuclei respectively. There was no correlation of percent p53 staining with gender, age, tumor stage, size, or histology. Lo cal, regional, and distant failures were observed in 12, 2, and 2 patients respectively. The 5-yr survival and DFS were 84% and 64% respectively. In u nivariate analysis, the only prognostic variable for survival was gender. F or DFS, advanced T category and large tumor size were predictive of poor DF S. In multivariate analysis, poor DFS was associated with high T category ( p = 0.0008), basaloid histology (p = 0.001), male gender (p = 0.002), and i ncreasing percent of p53 protein expression (p = 0.01). Conclusions: It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal. For patients managed with combined XRT, 5-FU, and MMC, percent p53 protein expression is of prognostic value for DFS independent of other clinical fac tors such as T category, gender, and histology. (C) 1999 Elsevier Science I nc.