High Incidence of p53 Gene Mutation in Human Ovarian Cancer and Its Association with Nuclear Accumulation of p53 Protein and Tumor DNA Aneuploidy

Abstract

Using the poylmerase chain reaction and single‐strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common “epithelial” ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G→A and G→C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow‐cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P<0.01 and P<0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common “epithelial” type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy.

A P53 Genetic Polymorphism As A Modulator of Hepatocellular Carcinoma Risk in Relation to Chronic Liver Disease, Familial Tendency, and Cigarette Smoking in Hepatitis B Carriers

“…The p53 tumor suppressor protein is involved in multiple central cellular processes, including gene transcription, DNA synthesis and repair, genomic stability, cell-cycle control, and apoptosis. [13][14][15][16][17][18][19][20] Loss of p53 function caused by genomic alterations or interaction with viral products has been suggested as a critical step in multistage hepatocarcinogenesis. 16,[21][22][23] Our data further suggest that a p53 genetic polymorphism was associated with the susceptibility to HCC among chronic HBV carriers.…”

“…[13][14][15][16][17][18][19][20] Loss of p53 function was associated with aneuploidy and increased cellular proliferation. [18][19][20] Mutations and deletions of the p53 gene have been identified in a large proportion of the tumor tissues from HCC patients. 16,21,22 A specific p53 mutation at codon 249 in exon 7 was associated with aflatoxin B 1 -induced HCC in certain areas of high aflatoxin B 1 contamination.…”

A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors

“…16,18,20,21,37,50,53,56,58 p53 was detected in 27 of 171 Stage I/II tumors (16%; 95% CI, 11-22%) and in 9 of 25 Stage III/IV tumors (36%; 95% CI, 18 -58%) (Fig. 4).…”

“…Mutation location was described in five of the eight studies in which exons 2-11 were screened. 50,107,115,118,125 Of the 100 mutations found in these studies, 7 were located outside exons 5-8 (5 in exon 4, 1 in exon 2, and 1 in exon 11).…”

“…19,20,[23][24][25]28,29,39,42,46,[49][50][51]53,58,[61][62][63][64]66,[71][72][73][74][76][77][78][79]82,83,85,87,90,95,97,99,103,104,106,109,110,114 Overall, p53 was detected in 39% of the Stage I/II tumors and 55% of the Stage III/IV tumors ( Again, although antibody specific estimates by tumor grade varied considerably (data not shown), a consistent pattern emerged. Overall, the proportion of tumors positive for p53 was lowest among the Grade 1 tumors and highest among the Grade 3 tumors (Fig.…”