P53 GENE-MUTATIONS AND MDM2 AMPLIFICATION ARE UNCOMMON IN PRIMARY CARCINOMAS OF THE UTERINE CERVIX

The p53 gene is the most frequently altered gene known thus far in a w ide variety of human cancers. Inactivation of p53, either through muta tion or through interaction with the human papillomavirus (HPV) E6 onc oprotein, is a characteristic feature of all cervical carcinoma cell l ines that have been studied. These findings suggest that p53 inactivat ion is required for cervical carcinoma development and that HPV infect ion and p53 mutation may be mutually exclusive. We have studied the p5 3 gene in 35 primary cervical carcinomas. DNA sequence and single stra nd conformational polymorphism analyses were used to evaluate p53 in 2 7 squamous carcinomas (25 HPV-positve) and eight adenocarcinomas (four HPV-positive). A missense mutation of p53 was observed in one HPV 16- positive squamous carcinoma, demonstrating that p53 mutations can occu r in combination with HPV infection. The HPV-negative tumors all lacke d p53 gene mutations. The absence of p53 mutations in HPV-negative cas es prompted an assessment of tumors for MDM2 gene amplification. The M DM2 gene encodes a p53 binding protein and has been found to be amplif ied in some human tumors lacking p53 mutations. MDM2 amplification was not identified in any of the tumors we examined, including four HPV-n egative cases. Our findings show that HPV infection and p53 gene mutat ion are not mutually exclusive and suggest that many HPV-negative carc inomas may arise via a pathway independent of p53 inactivation.