1. p53 mutations and p53, Waf-1, Bax and Bcl-2 expression in field cancerization of the head and neck
- Author
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Lavieille, J., gazzeri, sylvie, RIVA, C., Reyt, E., Brambilla, C, Brambilla, E, Service d'ORL, CHU Nord, Laboratoire de Biomécanique Appliquée (LBA UMR T24), Aix Marseille Université (AMU)-Université Gustave Eiffel-Aix Marseille Université (AMU)-Université Gustave Eiffel, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Politecnico di Milano [Milan] (POLIMI), Department of Otolaryngology and Head and Neck Surgery, University Hospital of Grenoble, BP 217, 38043, Grenoble Cedex 09, France, Université Joseph Fourier - Grenoble 1 (UJF), INSERM U1209, Institute for Advanced Biosciences, and DEIB, Politecnico di Milano, Milano, Italy
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Polymerase Chain Reaction ,Risk Factors ,Cyclins ,Proto-Oncogene Proteins ,Humans ,Neoplasm Invasiveness ,Polymorphism, Single-Stranded Conformational ,bcl-2-Associated X Protein ,Hyperplasia ,Mucous Membrane ,Smoking ,Exons ,Genes, p53 ,Gene Expression Regulation, Neoplastic ,Alcoholism ,Proto-Oncogene Proteins c-bcl-2 ,Head and Neck Neoplasms ,Mutation ,Carcinoma, Squamous Cell ,Tumor Suppressor Protein p53 ,Precancerous Conditions ,Carcinoma in Situ - Abstract
International audience; Squamous cell carcinomas of the Head and Neck (SCCHN) are related to carcinogens and proceed through multiple genetic and morphological steps. The aim of this study was to establish the status of p53 gene and p53-regulated proteins (Bax, Bcl-2 and Waf-1) expression in head and neck simultaneous preneoplastic and invasive lesions from patients with chronic alcohol and tobacco exposure. PCR-SSCP analysis of p53 gene and immunohistochemical analysis of Waf-1, Bax and Bcl-2 proteins were performed in 30 representative microdissected samples of mucosa exposed to carcinogens and preneoplastic or invasive lesions from 8 patients. P53 mutations were detected in all steps of carcinogenesis, but not in normal mucosa without carcinogen exposure. P53 mutations were different and multiple in concomittant areas of mucosa exposed to carcinogens, preneoplastic and invasive lesions at distant locations. Waf-1 and Bax protein expression was found in 100% of biopsies. Bcl-2 presented as basal cell positive staining in 95% of normal and preinvasive lesions and was overexpressed in only 30% of tumors, independently of p53 gene status. Bax/Bcl-2 ratio was > 1 in all premalignant lesions and < 1 in tumor samples only. There is evidence for the early, polyclonal origin of synchronous multiple preneoplastic and neoplastic lesions in the cancerization field. A P53 independent pathway seems to be implicated in Waf-1, Bax and Bcl-2 expression with an inversion of the Bax/Bcl-2 ratio restricted to invasive carcinomas.
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- 1970