Correlation of p53 mutations with epidermal growth factor receptor overexpression and absence of mdm2 amplification in human esophageal carcinomas.
Esophageal carcinomas from 24 patients, most of whom were smokers and consumed alcoholic beverages daily, were analyzed for mutations in exons 5-8 of the p53 tumor suppressor gene. Mutations were identified by polymerase chain reaction amplification and direct sequencing in 12 of 24 (50%) of the samples; almost half of the mutations were at A:T base pairs. Nuclear accumulation of p53 protein, determined by immunohistochemistry with the CM-1 polyclonal antibody, was observed in all cases in which a missense mutation in the p53 gene was detected. None of the 24 carcinomas had amplification of the mdm2 gene, an alternate pathway to p53 loss of function. Alterations involving three other cancer-related genes associated with human esophageal carcinogenesis, c-erbB-1/epidermal growth factor receptor (EGFR), c-myc, and retinoblastoma (Rb), were examined by Southern blot or immunohistochemical analysis in the same sample set to explore the possibility of a link between oncogene activation and loss of tumor suppressor function. While no associations were observed between amplification of the c-myc or EGFR genes and p53 abnormalities, a significant correlation (P < 0.01) was seen between the presence of p53 mutation and EGFR overexpression. Absence of Rb protein, measured immunohistochemically, was observed in four tumors, none of which had aberrations of the p53 gene.
Esteve
A
A
International Agency for Research on Cancer, Lyon, France.
Lehman
T
T
Jiang
W
W
Weinstein
I B
IB
Harris
C C
CC
Ruol
A
A
Peracchia
A
A
Montesano
R
R
Hollstein
M
M
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000648:ultrastructure*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D016161:Genes, Retinoblastoma / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; D066246:ErbB Receptors