p53 expression in locally advanced pharyngeal squamous cell carcinoma

Background: Prognosis for advanced head and neck squamous cell carcinoma re mains poor despite advances in treatment, although a small number of patien ts may benefit from induction therapy leading to increased local control. M utations of the p53 gene, which are present in a considerable percentage of head and neck squamous cell carcinomas, have been associated with poor res ponse to chemotherapy. The role of p53 protein overexpression (which is ass ociated with p53 gene mutations) in predicting the response to chemotherape utic agents and survival rates is not clear. Objective: To determine the association of p53 expression with chemotherapy response rates and disease-free survival rates in 62 patients with locally advanced pharyngeal cancer treated with induction cisplatin-5-fluorouracil chemotherapy between 1983 and 1995. Design: Historical cohort. Archival tissue from biopsies done before chemot herapy was immunohistochemically stained for the p53 tumor suppressor gene (clone D0-7; DAKO Corp, Glostrup, Denmark). Results: Positive staining for p53 occurred in 45 (73%) of 62 cases, with t he percentage of reactive cells ranging from 35% to 98%. Chemotherapy respo nse rates were higher in the p53-negative group (15/17 [88%]) compared with the p53-positive group (27/45 [60%]) (P = .07). The risk of recurrence was lower in the p53-negative group compared with the p53-positive group at 2, 3, and 5 years after treatment (P = .03, P = .01, and P = .007, respective ly). The median relapse-free survival rates of patients in the p53-negative group was 16 months, whereas those with p53 protein expression demonstrate d a median relapse-free survival lime of 9 months (P = .07). In multivariat e analyses, the only independent fatter of relapse-free survival rates was age older than 70 years. Conclusion: The present study shows a trend favoring p53 overexpression as a predictive and prognostic factor in locally advanced pharyngeal cancer tr eated with induction chemotherapy.