A pilot study has established that P53 over-expression is present in tissue from women with four or more components of fibrocystic disease. A cohort study involving human subjects is proposed to validate the hypothesis that women with components of fibrocystic disease whose tissue, by histochemical evaluation, over-expresses the mutant form of P53 with nuclear localization, are at significantly increased risk to breast cancer development. The evaluation will have two components and will utilize a unique tissue resource consisting of over 400 cryopreserved surgical samples from women with benign breast disease collected between 1973 and 1976. The tissue, which we have demonstrated to be in an excellent state of preservation, will be sectioned and histochemically evaluated for the presence and localization of mutant and wild type protein encoded by the tumor suppressor gene TP53, utilizing two well-characterized antibodies. One antibody identifies an N-terminal determinant in both mutant and wild type P53 protein. When utilized under nondenaturing conditions, the second antibody identifies only mutant P53 protein. The second component of the study will involve location of the women whose tissues were retrospectively analyzed, and defining their outcome with respect to breast cancer development in the intervening 15-18 years. This component will include SEER registry search, and physician and patient contact to determine if or when breast cancer occurred. Pilot studies and comparison with studies conducted over similar time intervals in similar geographic locations suggest that information on 80-85% of the cases will be retrievable. The study should provide a statistically valid assessment to define potential factors of increased risk of breast cancer development attributed to P53 over-expression. A current cohort of 500 women undergoing surgery for breast mass removal will be evaluated in parallel as described, with respect to components of fibrocystic disease and P53 over-expression. This study will first expand that which provided data for generation of the original hypothesis, and second, by comparison to data obtained with the 73-76 cohort, validate that a similar distribution of P53 over-expression exists within the current female population, for whom both lifestyles and diagnostic approaches have changed significantly.
NIH ExPorter
NIH ExPorter