The high mortality rate due to ovarian cancer is attributed to the lack of an effective early detection method. Due to the non-specificity of symptoms at early stage, most of the ovarian cancer cases are detected at late stages. This makes the access to women with early stage disease problematic and presents a barrier to development and validation of tests for detection of early stage of ovarian cancer in humans. Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Laying hen is the only available animal that develops ovarian cancer spontaneously; however, detail information on ovarian tumor histology is not available. The goal of this study was to determine the histological features of malignant ovarian tumors in laying hens. A total of 155 young and old (1-5 years of age) laying hens (Gallus domesticus) were selected randomly and evaluated gross and microscopically for the presence of ovarian tumors. Histological classification of tumors with their stages and grades were performed with reference to those for humans. Similar to humans, all four types including serous, endometrioid, mucinous and clear cell or mixed carcinomas were observed in hen ovarian tumors. Some early neoplastic as well as putative ovarian lesions were also observed. Similarities in histology, metastasis and stages of hen ovarian cancer to those of humans demonstrate the feasibility of the hen model for additional delineation of the mechanism underlying ovarian carcinogenesis, preclinical testing of new agents for the prevention and therapy of this disease. Keywordsovarian cancer; preclinical model; laying hen; tumor histology Ovarian cancer (OVCA) is a fatal disease of women with the highest mortality rate of all gynecological malignancies. Approximately 70% of women with OVCA die of this disease (1,2). Survival is high in women who present with early stage disease(3,4). The lack of specific symptoms, the relative inaccessibility of the ovaries deep in the pelvis, and the absence of NIH Public Access Author ManuscriptInt J Gynecol Cancer. Author manuscript; available in PMC 2010 May 1. Published in final edited form as:Int J Gynecol Cancer. 2009 May ; 19(4): 531-539. doi:10.1111/IGC.0b013e3181a41613. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript specific marker(s) represent barriers for early detection (5,6). In most cases, OVCA is diagnosed at a late stage(3). Furthermore, our understanding of the early pathogenesis of OVCA has been hindered by the lack of sufficient number of patients with early stage disease (3,4,7). Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Although large domestic mammals including bovine have similar reproductive traits and develop OVCA spontaneously similar to humans, the low incidence rate, multiple pregnancies, longer gestation and lactation period make them an inappropriate model for human OVCA. On the other hand, a number of rodent models, induced or g...

Cyclooxygenase (COX) (PTGS) is the rate-limiting enzyme in the biosynthesis of prostaglandins. Two COX isoforms have been identified, COX-1 and COX-2, which show distinct cell-specific expression and regulation. Ovarian cancer is the most lethal gynecological malignancy and the © Humana Press Inc. 2008 Correspondence to: Dale Buchanan Hales, dbhale@uic.edu. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript disease is poorly understood due to the lack of suitable animal models. The laying hen spontaneously develops epithelial ovarian cancer with few or no symptoms until the cancer has progresses to a late stage, similar to the human disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in the ovaries of normal hens and in hens with ovarian cancer. The results demonstrate that COX-1 was localized to the granulosa cell layer and cortical interstitium, ovarian surface epithelium (OSE) and postovulatory follicle (POF) of the normal ovary. In ovarian cancer, COX-1 mRNA was significantly increased and COX-1 protein was broadly distributed throughout the tumor stroma. COX-2 protein was localized to the granulosa cell layer in the follicle and the ovarian stroma. COX-2 mRNA expression did not change as a function of age or in ovarian cancer. There was significantly higher expression of COX-1 mRNA in the first POF (POF-1) compared to POF-2 and POF-3. COX-2 mRNA expression was not significantly different among POFs. There was no difference in COX-1 or COX-2 mRNA in the OSE isolated from individual follicles in the follicular hierarchy. The results confirm previous findings of the high expression of COX-1 in ovarian tumors further supporting the laying hen as a model for ovarian cancer, and demonstrate for the first time the high expression of COX-1 in POF-1 which is the source of prostaglandins needed for oviposition.

Transvaginal sonography can be used to determine ovarian status in hens. It offers the ability to make repeated examinations on the same hen to monitor early changes in the ovary associated with ovarian cancer.

Anti-tumor antibodies have potential as cancer biomarkers. There is relatively limited identification of anti-tumor antibodies in response to ovarian cancer, compared with studies for other cancers. There is also very limited information on the prevalence of anti-tumor antibodies among ovarian cancer patients. Although most anti-tumor antibodies react with antigens common to both tumor and normal tissue, the anti-tumor response tends to be confined to individuals with ovarian cancer, similar to other cancers. Antibodies to HOXA7, a differentiation antigen, have the highest reported prevalence in ovarian cancer (67%). Antibodies to other ubiquitous antigens including NY-ESO-1, Ep-CAM (epithelial cell adhesion molecule), HSP-90 (heat shock protein 90), and mutated p53 have been identified in ovarian cancer. Anti-tumor antibody specificity reflects the heterogeneity of antigen expression in tumors. Tests based on panels of a combination of anti-tumor antibodies may be more predictive for ovarian cancer, as no single specificity accounts for ovarian tumors. In addition to characterization of anti-tumor antibodies as diagnostic markers, study of anti-tumor antibodies is likely to provide insights into mechanisms of tumor development. There is evidence of antibodies to tumor antigens and of activated T cells, suggesting immune recognition of tumor antigens occurred. Nonetheless, as tumors are not 'rejected', it is likely that there are alterations in the immune system. The basis for tumor growth in the face of immune activity remains to be determined.

Objective With the exception of the laying hen, no other animal model of spontaneous ovarian surface epithelial cancer replicates the human disease. Flaxseed is the richest vegetable source of omega-3 fatty acids, which are chemopreventative in breast cancer and may be important in other cancers. The objective of this study was to determine if a flaxseed enriched diet had a chemopreventative effect on ovarian cancer in the laying hen. Methods White leghorn hens were fed a 10% flaxseed enriched or standard diet for one year. The incidence and severity of ovarian cancer were determined by gross pathology and histology in the two groups. General health markers were also measured. Eggs were collected and analyzed by gas chromatography to determine omega-3 fatty acid levels. Results A significant reduction in late stage ovarian tumors was detected in the flaxseed fed hens. Incidence rates of ovarian cancer were not significantly different between the two groups. The results indicate that a flaxseed diet increases overall survival in the laying hen. Flaxseed fed hens’ eggs incorporated significantly more omega-3 fatty acids compared to control hens. Conclusions These findings show that 10% flaxseed supplementation for one year in the laying hen results in a significant reduction in the severity of ovarian cancer, but no change in the incidence of the disease. Hens fed flaxseed had overall better health and reduced mortality. These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women.