PRETREATMENT P53 PROTEIN EXPRESSION CORRELATES WITH DECREASED SURVIVAL IN PATIENTS WITH END-STAGE HEAD AND NECK-CANCER

Relatively little is known about p53 changes in far-advanced head and neck cancer for several reasons: (a) most patients respond well to ini tial treatment; (b) most institutions do not encounter large numbers o f these patients; (c) recurrent or metastatic disease is often within body cavities inaccessible for analysis; and (d) the variety of treatm ent regimens and disease sites makes meaningful conclusions difficult to draw in such a heterogeneous group, The purpose of this study was t o evaluate the clinical significance of p53 mutations and overexpressi on in a homogeneous group of patients with end-stage squamous cell car cinoma of the head and neck. Pretreatment tumor specimens from a homog eneous group of 16 patients with end-stage squamous cell carcinoma of the head and neck were obtained, All patients had recurred after surge ry and radiation +/- induction chemotherapy, and all met the criteria for enrollment in a Phase II chemotherapy trial consisting of 5-fluoro uracil, N-phosphoacetyl-L-aspartate, and recombinant IFN-alpha. Each w as analyzed for mutations in exons 5-8 of the p53 gene and protein exp ression using the p53 polyclonal antibody CM-1. No relationship was fo und between p53 immunostain or p53 mutations and age, gender, site of primary tumor, or site of disease recurrence, p53 alterations also did not correlate with response to Phase II chemotherapy. p53 immunostain (but not p53 mutations) correlated with a shorter survival (P = 0.012 4) after diagnosis with end-stage disease, This suggests that mechanis ms other than p53 mutations which alter the half-life of p53 protein m ay contribute to the outcome of these patients.