P53 GENE MUTATION IS RARE IN HUMAN CERVICAL CARCINOMAS WITH POSITIVE HPV SEQUENCES

Chromosome 17p allelic losses and concurrent p53 mutations have been d emonstrated in various human cancers. We therefore investigated the pr esence of chromosome 17p allelic loss and possible concurrent p53 muta tion in 29 Korean cases of cervical carcinoma by restriction fragment length polymorphism (RFLP) analysis and polymerase chain reaction-sing le strand conformation polymorphism (PCR-SSCP) over the region from ex on 4 to exon 9 of the p53 gene. We also examined the expression of p53 in paraffin tissues by immunohistochemical staining and determined th e incidence of human papillomavirus (HPV) sequences in the same tissue s by multitype PCR analysis to correlate them to the allelic loss on c hromosome 17p13 and p53 mutation. In the analysis of 29 cases, loss of heterozygosity (LOH) was observed in eight (40%) cases out of 20 info rmative cases and p53 mutation was observed in only one case (3.4%) at exon 5. So in the majority of cases with LOH on 17p in this series, m utation of p53 gene appeared to be rare. But we obtained three cases ( 10.3%) of positive immunoreactivity from 29 eases. Those cases may car ry mutations outside of the regions examined by PCR-SSCP. HPV DNA was detected in 27 of 29 cases (93.1%). HPV types 8, 11, 16, and 18 were d etected in the samples we tested, while only two (7.4%) out of 27 HPV positive cases exhibited overexpression for p53 without any demonstrab le p53 mutation upon PCR-SSCP. These results suggest that HPV infectio n may play a role in inactivating wild-type p53 protein in cervical ca rcinomas. In conclusion, mutation and overexpression of p53 gene appea r to be rare, particularly in cases of cervical carcinoma associated w ith positive HPV sequence.