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.

Medienart:

Artikel

Erscheinungsjahr:

1998

Erschienen:

1998

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

Anticancer research - 18(1998), 6B vom: 22. Nov., Seite 4741-9

Sprache:

Englisch

Beteiligte Personen:

Lavieille, J P [VerfasserIn]
Gazzeri, S [VerfasserIn]
Riva, C [VerfasserIn]
Reyt, E [VerfasserIn]
Brambilla, C [VerfasserIn]
Brambilla, E [VerfasserIn]

Themen:

BAX protein, human
Bcl-2-Associated X Protein
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Journal Article
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
Research Support, Non-U.S. Gov't
Tumor Suppressor Protein p53

Anmerkungen:

Date Completed 29.01.1999

Date Revised 15.11.2006

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM098267914