p53 mutations and p53, Waf-1, Bax and Bcl-2 expression in field cancerization of the head and neck.
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.
Lavieille
J P
JP
Lung and Airways Cancer Research Group, A. Bonniot Institute, Faculté de Médecine, Grenoble, France.
Gazzeri
S
S
Riva
C
C
Reyt
E
E
Brambilla
C
C
Brambilla
E
E
D000437:Alcoholism / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis / Q000235:genetics*; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein