Abstract
Ovarian high grade serous carcinoma (HGSC) is a lethal form of ovarian cancer (OVCA). In most cases it is detected at late stages as the symptoms are non-specific during early stages. Emerging information suggests that the oviductal fimbria is a site of origin of ovarian HGSC. Currently available tests cannot detect ovarian HGSC at early stage. The lack of a preclinical model with oviductal fimbria that develops spontaneous ovarian HGSC is a significant barrier to developing an early detection test for this disease. The goal of this study was to examine if the oviductal fimbria in hens is a site of origin of HGSC and whether it expresses several putative markers expressed in ovarian HGSC in patients. A total of 135 laying hens (4 years old) were selected from a flock using transvaginal ultrasound (TVUS) imaging, followed by euthanasia and gross examination for the presence of solid masses and ascites. Histological types of carcinomas were determined by hematoxylin and eosin staining. Expression of WT-1, mutant p53, CA-125, PAX2 and Ki67 in normal or malignant fimbriae or ovaries were examined using immunohistochemistry, immunoblotting and gene expression assays. This study detected tumors in oviductal fimbriae in hens and routine staining revealed ovarian HGSC-like microscopic features in these tumors. These tumors showed similarities to ovarian HGSC in patients in expressing several markers. Compared with normal fimbriae, intensities of expression of WT-1, mutant p53, CA-125, and Ki67 were significantly (P<0.05) higher in fimbrial tumors. In contrast, expression of PAX2 decreased gradually as the tumor progressed to late stages. The patterns of expression of these markers were similar to those in ovarian HGSC patients. Thus, tumors of the oviductal fimbria in hens may offer a preclinical model to study different aspects of spontaneous ovarian HGSC in women including its early detection.
Highlights
Due to the non-specificity of symptoms at early stages, aggressive rates of growth, and the lack of an effective early detection test, high-grade serous carcinoma (HGSC) of the ovary, a fatal form of epithelial ovarian cancer (OVCA), in most cases is detected at late stages [1]
This study showed that oviductal fimbrial epithelium in laying hens may become malignant and develop tumor masses
These tumors showed similarities in their microscopic features and in the expression of molecular markers including Wilms Tumor 1 (WT-1), p53, CA-125, PAX2, and Ki67 to those observed in ovarian high grade serous carcinoma (HGSC) in women
Summary
Due to the non-specificity of symptoms at early stages, aggressive rates of growth, and the lack of an effective early detection test, high-grade serous carcinoma (HGSC) of the ovary, a fatal form of epithelial ovarian cancer (OVCA), in most cases is detected at late stages [1]. The 5-year survival rates of OVCA patients decrease to less than 30% when the disease is detected at late stages as opposed to more than 90% when detected at early stages [2]. Early detection of ovarian HGSC remains critical for improving the rates of survival of patients.
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