Gestational Trophoblastic Disease and Ovarian Carcinogenesis
Working closely with Dr. Donald P. Goldstein and Marilyn Bernstein, MHP, we are studying the natural history, epidemiology, treatment, and molecular biology of gestational trophoblastic disease. In collaboration with Drs. Shu-Wing Ng, Michael Muto, and Daniel Cramer, we are also pursuing studies of the genetic changes in invasive epithelial ovarian cancer, borderline ovarian tumors, and peritoneal malignancy. The Gynecologic Oncology Laboratory focuses on determining the early genetic changes in the development of ovarian cancer. Using DNA microarray technology, we have identified several promising markers including prostasin and osteopontin, which are elevated in the serum of patients with early ovarian cancer and significantly improve the sensitivity and specitivity of CA125 in the detection of ovarian cancer. Important advances have also been made in the understanding of the early genetic changes in ovarian cancer. Mucinous ovarian cancer is often associated with benign and borderline malignant mucinous epithelium in the same tissue. The same K-ras mutation has been demonstrated in adjacent benign, borderline malignant, and malignant mucinous epithelium in tissues precisely isolated by laser capture microscopy. K-ras mutation may be an early event in mucinous ovarian tumorigenesis, and benign and borderline mucinous epithelium may be a precursor of mucinous carcinoma. Patients with borderline serous ovarian cancer may later develop invasive serous ovarian cancer. By studying p53 and K-ras mutations, we have found that serous borderline ovarian tumor and subsequent invasive serous carcinomas seem to be unrelated. Patients with BRCA1 or BRCA2 mutations have a 20% to 40% risk of developing ovarian cancer and, therefore, prophylactic oophorectomy has been advocated as a preventive strategy. Importantly, papillary serous peritoneal cancer may also develop in patients with BRA1 and BRA2 mutations, and ovaries removed prophylacticly may already harbor occult ovarian malignancy. Placental site trophoblastic tumor (PSTT) is an unusual variant that is relatively resistant to chemotherapy. Based on our clinical experience, patients with nonmetastatic PSTT should undergo hysterectomy as primary therapy. Patients with gestational trophoblastic tumors are commonly cured with chemotherapy while preserving their fertility. Data from more than 500 patients who became pregnant following chemotherapy indicate that the outcome from these pregnancies is about the same as the general population.