Loss of heterozygosity and overexpression of the p53 gene in ovarian carcinoma.
Mutation and allelic loss of the p53 gene have been demonstrated in a variety of human cancers. In this study, DNA was extracted from formalin-fixed paraffin sections of ovarian carcinoma from 33 patients informative for a restriction fragment length polymorphism (RFLP) for BstU 1 within the 4th exon of the p53 gene. Allelic loss of p53 as indicated by loss of heterozygosity for this RFLP was demonstrated in 16/33 cases (48%). Because immunoreactivity for p53 correlates closely with the presence of mutation in the p53 gene, we performed immunohistochemical staining with the monoclonal antibody PAb1801. Diffuse nuclear p53 immunoreactivity was observed in 16 of the 33 (48%) informative cases used for loss of heterozygosity analysis (37/80 (46%) cases of ovarian carcinoma overall). A significant correlation (Fisher's exact test, P = 0.04) was observed between p53 overexpression and allelic loss. We found no evidence of association of p53 allelic loss or overexpression with advanced stage or other clinical or pathologic prognostic parameters. We conclude that mutation and allelic loss of p53 are common and probably related events in the development of ovarian carcinoma. This study demonstrates the use of paraffin sections in the analysis of p53 alterations in neoplasia.
Frank
T S
TS
Department of Pathology, University of Michigan Medical School, Ann Arbor.
Bartos
R E
RE
Haefner
H K
HK
Roberts
J A
JA
Wilson
M D
MD
Hubbell
G P
GP
D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D005260:Female; D016158:Genes, p53 / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
D016159:Tumor Suppressor Protein p53