OBJECTIVES:

• Identify women at increased risk for developing ovarian cancer.
• Identify and develop highly sensitive and specific tumor markers for the detection of early rather than advanced stage ovarian cancer.
• Develop ovarian cancer specific therapies based on increased understanding of the process of metastatic dissemination using newly developed molecular, genetic, and biochemical insights.
• Determine whether the use of minimally invasive office diagnostic laparoscopy and the "Ovarian Pap Test" can accurately differentiate normal, dysplastic, and malignant ovarian epithelium in women at increased risk for developing ovarian cancer.
• Determine the utility of molecular technologies to augment cytopathologic investigation in determining epithelial abnormalities in the interpretation of the "Ovarian Pap Test".

OUTLINE: This is a multicenter study.

Participants complete quality of life and psychosocial questionnaires at the initial visit. Asymptomatic women without recognized ovarian pathology complete an extensive personal and family medical history questionnaire before the initial visit and meet with a genetic counselor.

Blood specimens are collected and analyzed for recently identified experimental ovarian cancer markers such as lysophospholipids (LPA), epidermal growth factor receptors (EGFRs), soluble urinary type plasminogen activator (suPAR), and matrix metalloproteinases (MMPs). Since tumor markers are considered experimental, results are not reported to study participants.

"Ovarian Pap Test" is a new diagnostic test to detect pre-cancerous or early changes on the ovaries. Using minimally invasive office laparoscopy, the "Ovarian Pap Test" involves direct visualization of the ovaries and collection of cells from the surface of the ovary and from the peritoneal cavity by the use of a laparoscopic cytologic sampling instrument.

Participants who undergo prophylactic bilateral salpingo-oophorectomy have tissue collected for genomic and molecular analysis.

Ovarian organ cultures are analyzed for proliferation/apoptosis, cell cycle abnormalities and control defects, and processes of cellular migration and invasion. PCR-based assays specifically focusing on expression of mutant forms of p53, variant EGFRs, telomerase, MMPs, and microsatellite instability are performed.

Participants are followed every 6 months.

PROJECTED ACCRUAL: A total of 6,000 participants (5,000 at increased risk and 1,000 with newly diagnosed cancer) will be accrued for this study within 5 years.