The data collected and analyzed in the Registry provide the sole comprehensive series of cases of DES-associated clear cell adenocarcinoma (CCA) of the vagina and/or cervix in women born after 1948 for comparative and collaborative study. Both DES-exposed and unexposed patients are accessioned. The Tissue Bank of fixed specimens from patients treated for CCA along with fresh tissue from newly diagnosed and/or recurrent cases will be maintained and expanded. An established Advisory Board of external investigators will meet regularly with to oversee the distribution of these rare tissues to qualified investigators for molecular studies. The success of these initial efforts has led to a new collaborative project with Dr. G. Cunha of UCSF, who, using fresh CCA tissue supplied by Registry patients, has established a human CCA transplant cell line. His laboratory will evaluate growth and differentiation requirements of CCA as well as identify the role of the stroma in these processes and test the response of CCA to estrogen with the goals of gaining a better understanding of the molecular regulations of these malignancies and the potential development of new therapeutic strategies. Collaborative work regarding the induction of microsatellite instability and down-regulation of DNA mismatch repair gene expression with Dr. Jeff Boyd, of MKSCC, is also being proposed. The hypothesis is that the induction of microsatellite instability represents a critical component of the molecular mechanism through which DES initiates carcinogenesis. Preliminary data indicate there may be a secondary rise in the age incidence curve developing in DES-exposed patients over the age of 40 years, similar to what is observed in the unexposed population. The possible early detection of such a rise will be tested. If detected, this would provide important public health information to the DES-exposed population since many physicians have erroneously assumed that patients over age 30 years are not at risk for CCA. With Dr. J. Palmer of the Boston University School of Medicine, epidemiologic studies will be performed to evaluate factors that contribute to the development of the disease in older DES-exposed (over age 35 years) and also the reasons for late recurrences of CCA (beyond 5 years).