Ovarian adenocarcinomas in the laying hen and women share similar alterations in p53, ras, and HER-2/neu.
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.
Hakim
Amy A
AA
Division of Gynecologic Oncology, Evanston Northwestern Healthcare, Northwestern University, Evanston, Illinois, [corrected] USA.
Barry
Catherine P
CP
Barnes
H John
HJ
Anderson
Kenneth E
KE
Petitte
James
J
Whitaker
Regina
R
Lancaster
Jonathan M
JM
Wenham
Robert M
RM
Carver
Donna K
DK
Turbov
Jane
J
Berchuck
Andrew
A
Kopelovich
Levy
L
Rodriguez
Gustavo C
GC
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002645:Chickens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010057:Oviducts / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53