Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu
ABSTRACT We examined alterations in the p53 tumor suppressor gene and the ras and HER-2/neu oncogenes in chicken ovarian cancers to determine if these tumors have genetic alterations similar to those in human ovarian adenocarcinomas. Mutations in the p53 tumor suppressor gene and the H-ras and K-ras oncogenes were assessed by direct sequencing in 172 ovarian cancers obtained from 4-year-old birds enrolled at age 2 in two separate 2-year chemoprevention trials. Birds in trial B had approximately twice as many lifetime ovulations as those in trial A. Immunohistochemical staining for the HER-2/neu oncogene was done on a subset of avian ovarian and oviductal adenocarcinomas. Alterations in p53 were detected in 48% of chicken ovarian cancers. Incidence of p53 alterations varied according to the number of lifetime ovulations, ranging from 14% in trial A to 96% in trial B (P < 0.01). No mutations were seen in H-ras, and only 2 of 172 (1.2%) tumors had K-ras mutations. Significant HER-2/neu staining was noted in 10 of 19 ovarian adenocarcinomas but in only 1 of 17 oviductal adenocarcinomas. Similar to human ovarian cancers, p53 alterations are common in chicken ovarian adenocarcinomas and correlate with the number of lifetime ovulations. Ras mutations are rare, similar to high-grade human ovarian cancers. HER-2/neu overexpression is common and may represent a marker to exclude an oviductal origin in cancers involving both the ovary and oviduct.
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ABSTRACT: The laying hen model of spontaneous epithelial ovarian cancer (EOC) is unique in that it is the only model that enables observations of early events in disease progression and is therefore also uniquely suited for chemoprevention trials. Previous studies on the effect of dietary flaxseed in laying hens have revealed the potential for both amelioration and prevention of ovarian cancer. The objective of this study was to assess the effect of flaxseed on genes and pathways that are dysregulated in tumors. We have used a bioinformatics approach to identify these genes, followed by qPCR validation, immunohistochemical localization, and in situ hybridization to visualize expression in normal ovaries and tumors from animals fed a control diet or a diet containing 10% flaxseed.BMC Genomics 08/2014; 15(1):709. DOI:10.1186/1471-2164-15-709 · 4.04 Impact Factor
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ABSTRACT: Leiomyoma’s of the oviduct and its ventral ligament (VL) are common tumours of the domestic fowl which develop after the end of the first laying season. In the present study, macroscopic, microscopic, and immunohistochemical features of the leiomyomas of the reproductive tract and their prevalence were investigated in commercial laying hens. In 60-90 weeks old commercial laying hens, toward the end of the first laying period, the incidence of genital tract leiomyomas were determined as 10.43%. Of these, 95.81% were developed from oviduct VL and 4.19% were oviduct leiomyomas. These tumours were firm, round to oval and microscopically well-circumscribed, consisting of monomorphic spindle cells. In immunohistochemical examination with α-smooth muscle actin, desmin and vimentin, all tumours were found positive with these markers. To investigate the aetiological importance for tumourogenesis, the plasma concentrations of 17 β-oestradiol and progesterone levels were determined. Concentrations of 17 β-oestradiol and progesterone were higher in hens with tumours than that of non-tumour control animals. The results suggested that there was an association between the levels of 17 β-oestradiol and progesterone and the leiomyomas of genital tract in hens.Kafkas Üniversitesi Veteriner Fakültesi Dergisi 05/2014; 20(3):429-434. DOI:10.9775/kvfd.2013.10321 · 0.29 Impact Factor
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ABSTRACT: The chicken is a unique experimental model for studying the spontaneous onset and progression of ovarian cancer (OVC). The prevalence of OVC in chickens can range from 10-35% depending on age, genetic strain, reproductive history, and diet. Furthermore, the chicken presents epidemiological, morphological, and molecular traits that are similar to human OVC making it a relevant experimental model for translation research. Similarities to humans include associated increased risk of OVC with the number of ovulations, common histopathological sub-types including high-grade serous, and molecular-level markers or pathways such as CA-125 expression and p53 mutation frequency.Collectively, the similarities between chicken and human OVC combined with a tightly controlled genetic background and predictable onset window provides an outstanding experimental model for studying the early events and progression of spontaneous OVC tumors under controlled environmental conditions. This review will cover the existing literature on OVC in the chicken and highlight potential opportunities for further exploitation (e.g, biomarkers, prevention, treatment, and genomics).This article is protected by copyright. All rights reservedPROTEOMICS - CLINICAL APPLICATIONS 08/2014; 8(9-10). DOI:10.1002/prca.201300135 · 1.81 Impact Factor