P53 EXPRESSION - PREDICTING RECURRENCE AND 2ND PRIMARY TUMORS IN HEADAND NECK SQUAMOUS-CELL CARCINOMA

Background: The survival rate for head and neck squamous cell carcinom a remains poor despite therapeutic advances over the last two decades. For patients with disease confined to the head and neck, there are tw o major and biologically distinct patterns of treatment failures after definitive therapy: recurrence of primary disease and development of second primary tumors. Understanding the biological basis of patterns of treatment failure after definitive therapy is needed to guide the d evelopment of adjuvant treatment and strategies to prevent second prim ary tumors. Purpose: To determine whether expression of the p53 protei n has prognostic significance and/or is associated with patterns of tr eatment failure, we examined protein expression in primary tumor speci mens of patients with head and neck squamous cell carcinoma. Methods: Immunohistochemical analysis with a monoclonal antibody (D07) specific for p53 protein was used to detect expression of the protein in forma lin-fixed, paraffin-embedded tumor samples from 69 head and neck cance r patients treated with definitive local therapy (surgery and/or radio therapy) between January 1980 and October 1983 at The University of Te xas M. D. Anderson Cancer Center. We quantitated p53 protein expressio n and assessed its association with duration of patient survival, patt erns of treatment failure (recurrence of primary tumor and development of second primary tumor), and other clinical parameters. All reported P values resulted from two-sided statistical tests. Results: We found detectable levels of p53 protein expression in the tumor cell nuclei of 41 of 69 patients. Thirty-six (52%) of 69 patients whose tumors exh ibited p53 protein expression in greater than or equal to 10% of the c ell nuclei were grouped as p53 positive, and 33 (48%) of 69 patients w hose tumors exhibited less than 10% nuclear expression were grouped as p53 negative. The clinical characteristics of the patients in the p53 -positive and p53-negative groups were well balanced. Overall survival was significantly lower, and the times to tumor recurrence, to second primary tumors, and to any treatment failure were significantly short er in the p53-positive group than in the p53-negative group (P = .0002 , P = .047, P = .003, and P = .0009, respectively), mainly because the p53 positivity was associated with earlier development of tumor recur rence and second primary tumors. The rate of second primary tumor deve lopment per person per year was also significantly higher in the p53-p ositive group than in the p53-negative group. By use of multivariate a nalysis according to the Cox regression model, p53 expression status w as identified as the most significant predictor of overall survival du ration (P = .007), time to tumor recurrence (P = .053), time to second primary tumors (P = .035), and time to any treatment failure (P = .00 1). Conclusions: The expression of p53 protein in primary head and nec k squamous cell carcinoma was significantly predictive of shorter surv ival because of its association with earlier development of both tumor recurrence and second primary tumors. Thus, p53 expression may be a v aluable marker for identifying individuals at high risk of developing a recurrence of primary disease and second primary tumors who may bene fit from adjuvant therapy and chemoprevention after definitive local t herapy.