ANALYSIS OF P53 SERUM ANTIBODIES IN PATIENTS WITH HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Background: Mutation of the p53 tumor suppressor gene (also known as T P53) often leads to the synthesis of p53 protein that has a longer tha n normal half-life, Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techni ques, Serum antibodies directed against p53 protein (p53-Abs) have bee n detected in some cancer patients, Purpose: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) fo r the presence of p53-Abs, and we evaluated potential associations bet ween the presence of these antibodies and other histopathologic and cl inical features, Methods: Serum was collected from each patient at the time of diagnosis, In addition, tumor biopsy specimens were obtained before the initiation of treatment, An enzyme-linked immunosorbent ass ay was used to detect p53-Abs, The accumulation of p53 protein in tumo r cell nuclei was assessed immunohistochemically by use of the anti-p5 3 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy, Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier meth od; survival comparisons were made by use of the logrank statistic, Un ivariate and multivariate analyses were conducted to identify factors associated with survival, Reported P values are two-sided, Fifteen (18 .8%) of the 80 had p53-Abs, Tumor cell nuclei in 43 (58.9%) of 73 asse ssable biopsy specimens exhibited strong p53 immunostaining. Patient t reatment method and the accumulation of p53 protein in tumor cell nucl ei were not associated with increased risks of relapse or death, In un ivariate analyses, advanced tumor stage (>T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increas ed risk of death (P for trend = .007 and P = .002, respectively), wher eas advanced tumor stage, substantial regional lymph node involvement (>N1), and the presence of p53-Abs mere associated with an increased r isk of relapse (P for trend = .002, P = .02, and P < .0001, respective ly). In multivariate analyses, advanced tumor stage and the presence o f p53-Abs were significantly associated with increased risks of relaps e (P for trend = .04 and P = .003, respectively) and death (P for tren d = .03 and P = .03, respectively), At 2 years of follow-up, the overa ll survival proportion was 63% (95% confidence interval [CI] 47%-80%) when no p53-Abs were detected compared with 29% (95% CI 4%-54%) when p 53-Abs were detected, Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0% -31%) if p53-Abs were detected, Conclusions aizd Implications: The pro portion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein, Th e presence of p53-Abs is significantly associated with increased risks of relapse and death.