Hakim Amy A, Barry Catherine P, Barnes H John, Anderson Kenneth E, Petitte James, Whitaker Regina, Lancaster Jonathan M, Wenham Robert M, Carver Donna K, Turbov Jane, Berchuck Andrew, Kopelovich Levy, Rodriguez Gustavo C
Division of Gynecologic Oncology, Evanston Northwestern Healthcare, Northwestern University, Evanston, Illinois, [corrected] USA.
Cancer Prev Res (Phila). 2009 Feb;2(2):114-21. doi: 10.1158/1940-6207.CAPR-08-0065. Epub 2009 Jan 27.
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.
我们检测了鸡卵巢癌中p53肿瘤抑制基因以及ras和HER-2/neu癌基因的改变情况，以确定这些肿瘤是否具有与人类卵巢腺癌相似的基因改变。通过直接测序评估了172例卵巢癌中p53肿瘤抑制基因以及H-ras和K-ras癌基因的突变情况，这些卵巢癌取自参加两项为期2年的化学预防试验的2岁4岁鸡。试验B中的鸡一生排卵次数约为试验A中鸡的两倍。对一部分禽卵巢和输卵管腺癌进行了HER-2/neu癌基因的免疫组化染色。在48%的鸡卵巢癌中检测到p53改变。p53改变的发生率根据一生排卵次数而有所不同，从试验A中的14%到试验B中的96%（P<0.01）。在H-ras中未发现突变，172个肿瘤中只有2个（1.2%）有K-ras突变。在19例卵巢腺癌中有10例观察到显著的HER-2/neu染色，但在17例输卵管腺癌中只有1例有此染色。与人类卵巢癌相似，p53改变在鸡卵巢腺癌中很常见，并且与一生排卵次数相关。Ras突变很少见，类似于人类高级别卵巢癌。HER-2/neu过表达很常见，可能是排除涉及卵巢和输卵管的癌症起源于输卵管的一个标志物。
