P53 PROTEIN EXPRESSION AND GENE ANALYSIS IN CLEAR-CELL ADENOCARCINOMAOF THE VAGINA AND CERVIX

Objective: p53 is the most commonly mutated gene in human cancers. The objective of this study was to determine if clear cell adenocarcinoma s (CCAs) of the vagina and cervix are associated with p53 gene mutatio ns or alterations in p53 tumor-suppressor protein expression. Methods: Paraffin-embedded tissue specimens from 21 women (median age 22 years ) with clear cell adenocarcinoma of the vagina or cervix were studied. Fifteen women had a prior history of in utero exposure to diethylstil bestrol. p53 protein expression was detected by immunohistochemical (I HC) analysis with monoclonal antibody DO-7 (Dako Corp.) which recogniz es both wild-type and mutant p53 proteins. For p53 gene analysis, geno mic DNA from malignant tissue was isolated and exons 4-10 were amplifi ed by PCR and subjected to mutation screening by single-stranded confo rmation polymorphism (SSCP) analysis. Results: p53 protein was detecte d by MC in tumors from 14 of 21 cases (67%). The observed p53 staining patterns were heterogeneous in both the proportion and intensity of t umor cells stained but were clearly overexpressed relative to the surr ounding benign stroma. Metastatic tumors from 3 women with metastatic disease were also positive for p53 staining, SSCP analysis did not ide ntify p53 mutations in any of the cases and strongly suggests that the tumors contained only wild-type p53 alleles. Conclusions: Recent stud ies have demonstrated that wild-type p53 may accumulate in response to DNA damage which normally leads to growth arrest or programmed cell d eath. Our observations are consistent with the hypothesis that p53 ove rexpression in CCAs of the vagina and cervix is a response to generali zed DNA damage, rather than a result of p53 protein half-life prolonga tion resulting from mutational inactivation of p53. Overexpression of wild-type p53 protein in vaginal and cervical CCA may relate to the mo re favorable prognosis of this subset of tumors in comparison to other gynecologic tumors containing mutated p53 genes. (C) 1996 Academic Pr ess, Inc.