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.

Reduction of Ovarian and Oviductal Cancers in Calorie-Restricted Laying Chickens

“…In addition, the chicken has a high ovulatory rate (daily), raising the possibility that chicken and human OVACs have a common pathogenesis related to ovulation-induced genetic damage to ovarian epithelial cells. Importantly, we have recently shown that chicken ovarian adenocarcinomas have genetic or molecular features that are similar to those of human OVAC (34) and that the prevalence of alterations in p53 in chicken tumors correlated with the number of prior ovulatory events, These findings further support the concept that ovulation with repeated cycles of rupture and repair of the ovarian epithelium may increase the number of proliferative events and genetic errors.…”

Advantages of the avian model for human ovarian cancer

“…Moreover, the sequencing of the chicken genome 10 years ago enabled valuable molecular comparisons with human cases (71). Different biomarkers, such as CA-125, P53 and E-cadherin, were also expressed in EOC in both species (28,(72)(73)(74).…”

“…It is possible that structural differences in the ovarian surface epithelium between mice and humans (27) allow mice to develop a form of ̔resistance̓ against EOC development, despite their significantly higher ovulation rates. Interestingly, it is estimated that the number of ovulations of a 2-year-old hen is similar to the number of ovulations of a woman at menopause (28). The fact that the hen is the only animal model that develops spontaneous EOC suggests similarities in the role of ovulation in the development of the disease between hens and humans.…”

Leiomyomas of Oviduct and Its Ventral Ligament of Hens: Immunohistochemical Evaluation and the Plasma Concentration Levels of 17 β-Oestradiol and Progesterone

“…Although most genital organ leiomyomas in laying hens develop from the oviduct VL, occasional oviduct leiomyomas can also be seen [2] . In humans, uterine leiomyomas are the most common type of reproductive tract tumours in women and leiomyomas of the oviduct in sexually mature domestic hens share important features with human uterine leiomyomas [7][8][9] . The high prevalence and ability to induce leiomyomas of the oviduct VL in hens means that this species could be of interest as a model for the study of similar tumours in mammals as well as women because the remarkable similarities between the ovulatory cyles of women and hens [3,[7][8][9][10][11] .…”