The epidemiology of ovarian granulosa cell tumors: a case-control study.

OBJECTIVE: This study identified risk factors for ovarian granulosa cell tumors (GCT) through a case-control study comparing women with GCT to women with epithelial ovarian cancers (OC) and general population (GP) controls. METHODS: Women with GCT and OC were identified from our hospital tumor board and the Massachusetts and New Hampshire Statewide Cancer Registries between January, 1988 and November, 2008. Age, gender and county matched GP controls were identified through town books in Massachusetts and drivers' license lists in New Hampshire. Epidemiologic factors including age, race, obesity, pregnancy history, smoking, and family history were evaluated. Odds ratio (OR) was calculated and adjusted for race and age. RESULTS: Seventy-two women with GCT, 1578 GP controls, and 1511 OC controls were identified. Patients with GCT were significantly more likely to be non-white (OR 8.49; 4.07, 17.7), obese with a BMI >30 (OR 5.80; 3.01, 11.2), and have a family history of breast (OR 2.13; 1.19, 3.80) or ovarian cancer (OR 2.89; 1.08, 7.72) than GP controls. The risk of developing GCT was significantly decreased in women who smoked (OR 0.46; 0.27, 0.78), used oral contraceptive pills (OR 0.32; 0.17, 0.63) or were parous with 1-2 (OR 0.30; 0.16-0.56) or greater than 2 births (OR 0.50; 0.27, 0.94) when compared to GP controls. CONCLUSION: These findings suggest an independent association between non-white race and obesity as a hyperestrogenic state in the development of GCT while parity and OCP use may be protective. An unknown familial predisposition for GCT may exist.

Ovarian cancer in the proteomics era: diagnosis, prognosis, and therapeutics targets.

Ovarian cancer is clinically quiet as it plants seeds of metastases in the peritoneal cavity, even during early stages when there is highest potential for cure. The only available biomarker is CA125, which has an unacceptably low sensitivity and specificity for diagnostic use. Highly sensitive and specific tools to further optimize early diagnosis and treatment are needed. We propose that proteomic technologies have an important role to play in the development of these tools. Mass spectrometry platforms, such as surface-enhanced laser desorption/ionization time-of-flight, may be used to mine patient's serum for proteomic signatures that are shed by tumor and stroma. Such signatures could serve as a diagnostic tool during early-stage disease and as a remission-monitoring tool in later-stage disease. Reverse-phase protein microarrays are a new microproteomic tool to profile signaling pathways in ovarian cancer, thus identifying therapeutic targets while simultaneously suggesting prognostic indicators. Proteomic technologies have the capacity to build upon our genomic and clinical understanding of ovarian cancer by moving the focal point to the tumor and its microenvironment. This unique proteomic vantage point allows the creation of tools that will aid clinicians in making rational decisions in the diagnosis and treatment of women with ovarian cancer.

Differentiation of T cells in nude mice.

Cells bearing the T-cell differentiation alloantigens TL and Thy-1 were enumerated in preparations of spleen and lymph node cells of nu/nu mice. Healthy nu/nu mice had few or no demonstrable TL+ or Thy-1+ cells whereas mice with viral hepatitis, including some born of nu/nu X nu/nu matings, had many. Healthy nu/nu mice were treated daily with the thymic hormone thymopoietin or with ubiquitin, polypeptides that induce the differentiation of TL+Thy-1" cells from TL-Thy-1- precursors in vitro. After 14 days, 20 to 40 percent of their spleen cells were of the TL+Thy-1+ phenotype typical of thymocytes and 10 to 25 percent of their lymph node cells were TL-Thy-1+, typical of later T-cell differentiation. Similar frequencies of such cells were found in untreated nu/nu mice suffering from severe viral hepatitis. These data conform to the current view that prothymocytes are preprogrammed cells whose maturation to thymocytes, normally induced in the thymus by thymopoietin, can be triggered by other agents under abnormal circumstances. Tests of T-cell function were not included in this study.