title: Pretreatment p53 protein expression correlates with decreased survival in patients with end-stage head and neck cancer.
abstract: Relatively little is known about p53 changes in far-advanced head and neck cancer for several reasons: (a) most patients respond well to initial treatment; (b) most institutions do not encounter large numbers of these patients; (c) recurrent or metastatic disease is often within body cavities inaccessible for analysis; and (d) the variety of treatment regimens and disease sites makes meaningful conclusions difficult to draw in such a heterogeneous group. The purpose of this study was to evaluate the clinical significance of p53 mutations and overexpression in a homogeneous group of patients with end-stage squamous cell carcinoma of the head and neck. Pretreatment tumor specimens from a homogeneous group of 16 patients with end-stage squamous cell carcinoma of the head and neck were obtained. All patients had recurred after surgery and radiation +/- induction chemotherapy, and all met the criteria for enrollment in a Phase II chemotherapy trial consisting of 5-fluorouracil, N-phosphoacetyl-L-aspartate, and recombinant IFN-alpha. Each was analyzed for mutations in exons 5-8 of the p53 gene and protein expression using the p53 polyclonal antibody CM-1. No relationship was found 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 = 0.0124) after diagnosis with end-stage disease. This suggests that mechanisms other than p53 mutations which alter the half-life of p53 protein may contribute to the outcome of these patients.
authors.affiliation: Division of Population Science and Departments of Surgical Oncology, Biostatistics, and Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Sauter
authors.forename: J A
authors.initials: JA
authors.lastname: Ridge
authors.forename: S
authors.initials: S
authors.lastname: Litwin
authors.forename: C J
authors.initials: CJ
authors.lastname: Langer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000532:radiotherapy; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53