Our laboratory focuses on the pathobiology of cancer precursors in the female genital tract. These include pre-invasive neoplasms of the vulva, cervix, endometrium and distal fallopian tube. Lately our interests have centered on the novel concept that pelvic serous cancer, the most lethal "ovarian" cancer in women, arises in many instances from the distal fallopian tube. We have shown that a very high percentage of serous cancers arising in women with BRCA mutations emerge from the tubal fimbria and that the distal tube is a source for pelvic cancer in one half of women for whom BRCA status is unknown. A striking biologic alteration that occurs in normal appearing tubal mucosa and shares many features with serous cancer, termed the tubal "p53 signature", was described in our laboratory, and has emerged as the leading candidate precursor to pelvic serous cancer. We have recently shown that this precursor shares risk factors with ovarian cancer, strengthening further its status as an important early event in serous carcinogenesis. This discovery is the subject of several collaborative projects designed to determine 1) if the p53 signature is a surrogate risk factor for serous malignancy, 2) if it predates the malignancy, 3) the extent to which early maligancies arising in the fallopian tube contribute to tumors otherwise classified as ovarian or peritoneal serous carcinomas and 4) the biologic events that characterize precursor development and its transition to malignancy in women with BRCA mutations and the general population. Our hope is that a fully characterized precursor to pelvic serous cancer will encourage new directions in ovarian/fallopian tube detection and prevention.