Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu
Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu
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DOI：
10.1158/1940-6207.capr-08-0065
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发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Rodriguez, Gustavo C.
中科院分区：
文献类型：
--
作者：
Hakim, Amy A.;Barry, Catherine P.;Rodriguez, Gustavo C.
我们检测了鸡卵巢癌中p53肿瘤抑制基因、ras和HER-2/neu癌基因的改变，以确定这些肿瘤是否具有与人类卵巢腺癌相似的遗传改变。在两项独立的2年化学预防试验中，通过直接测序从2岁时登记的4岁鸟类中获得172例卵巢癌，评估了p53肿瘤抑制基因和H-ras和K-ras癌基因的突变。试验B中的鸟类一生的排卵次数大约是试验a中的两倍。HER-2/ new癌基因的免疫组织化学染色是在禽类卵巢和输卵管腺癌的一个子集上进行的。在48%的鸡卵巢癌中检测到p53基因的改变。p53改变的发生率随一生中排卵次数的不同而变化，从试验A的14%到试验B的96% （P < 0.01）。H-ras未见突变，172例肿瘤中仅有2例（1.2%）发生K-ras突变。19例卵巢腺癌中有10例可见HER-2/neu染色，17例输卵管腺癌中仅有1例可见HER-2/neu染色。与人类卵巢癌类似，p53的改变在鸡卵巢腺癌中很常见，并且与一生中排卵的次数有关。Ras突变是罕见的，类似于高级别的人类卵巢癌。HER-2/neu过表达是常见的，可能是排除卵巢和输卵管癌的一个标志。
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.