Purpose: To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy (XRT), 5-fluorouracil (5-FU), and mitomycin C (MMC).
Methods and materials: From January 1991 to December 1993, 58 consecutive patients 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/m2/day 1-4) and MMC (10 mg/m2 day 1) of each cycle of XRT. Paraffin-embedded tumor samples were unavailable in 9 patients, leaving 49 patients in the study. Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining. Actuarial survival and disease-free survival (DFS) rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. A Cox proportional hazard model was used for the multivariable analysis.
Results: There were 6 T1, 26 T2, 7 T3, and 10 T4 lesions. Primary tumor sizes ranged from 1-15 cm with a median of 4 cm. There were 6 patients with nodal metastases. Median follow-up was 4.5 years. Positive nuclear immunostaining 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. Local, 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 univariate analysis, the only prognostic variable for survival was gender. For DFS, advanced T category and large tumor size were predictive of poor DFS. 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 increasing 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 factors such as T category, gender, and histology.