caa a22 4500 39756239X CHVBK 20180308164819.0 cr unu---uuuuu 161202e19960904xx s 000 0 eng 10.1093/jnci/88.17.1228 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.17.1228 Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma [Elektronische Daten] [Jean Bourhis, Richard Lubin, Béatrice Roche, Serge Koscielny, Jacques Bosq, Isabelle Dubois, Monique Talbot, Patrick Marandas, Guy Schwaab, Pierre Wibault, Bernard Luboinski, François Eschwege, Thierry Soussi] Background: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohisto-chemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. Purpose: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical 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 assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 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 method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. Results: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (>T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (>N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend =.002, P = .02, and P<.0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (P for trend = .04 and P =.003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-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 and Implications: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death. [J Natl Cancer Inst 1996;88:1228-33] © Oxford University Press REPORTS nationallicence Bourhis Jean Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut Lubin Richard Institut de Génétique Moléculaire Paris aut Roche Béatrice Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut Koscielny Serge Department of Statistics, Institut Gustave-Roussy Villejuif, France aut Bosq Jacques Department of Pathology, Institut Gustave-Roussy Villejuif, France aut Dubois Isabelle Institut de Génétique Moléculaire Paris aut Talbot Monique Department of Pathology, Institut Gustave-Roussy Villejuif, France aut Marandas Patrick Department of Head and Neck Surgery, Institut Gustave-Roussy Villejuif, France aut Schwaab Guy Department of Head and Neck Surgery, Institut Gustave-Roussy Villejuif, France aut Wibault Pierre Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut Luboinski Bernard Department of Head and Neck Surgery, Institut Gustave-Roussy Villejuif, France aut Eschwege François Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut Soussi Thierry Institut de Génétique Moléculaire Paris aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/17(1996-09-04), 1228-1233 0027-8874 88:17<1228 1996 88 jnci https://doi.org/10.1093/jnci/88.17.1228 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.17.1228 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bourhis Jean Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Lubin Richard Institut de Génétique Moléculaire Paris aut NATIONALLICENCE 700 1- Roche Béatrice Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Koscielny Serge Department of Statistics, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Bosq Jacques Department of Pathology, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Dubois Isabelle Institut de Génétique Moléculaire Paris aut NATIONALLICENCE 700 1- Talbot Monique Department of Pathology, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Marandas Patrick Department of Head and Neck Surgery, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Schwaab Guy Department of Head and Neck Surgery, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Wibault Pierre Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Luboinski Bernard Department of Head and Neck Surgery, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Eschwege François Department of Radiation Oncology, Institut Gustave-Roussy Villejuif, France aut NATIONALLICENCE 700 1- Soussi Thierry Institut de Génétique Moléculaire Paris aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/17(1996-09-04), 1228-1233 0027-8874 88:17<1228 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford