Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers
Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers
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DOI：
10.1111/j.1440-1827.2004.01747.x
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发表时间：
2004-10-01
影响因子：
2.2
通讯作者：
Nakajima, T
中科院分区：
文献类型：
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作者：
Sano, T;Shimooka, H;Nakajima, T
14-3-3 sigma(Sigma)是一个主要的G2/M检查点控制基因，已证明其在多种癌症中的失活主要是通过表观遗传的超甲基化而不是通过基因改变。为确定14-3-3sigma蛋白与p16、P53蛋白在宫颈癌中的表达，采用免疫组织化学方法对不同组织学亚型的宫颈癌及不典型增生组织进行了检测。14-3-3sigma在宫颈不典型增生(17/17)和鳞癌(29/29)中均呈强阳性和弥漫性表达，包括HPV阴性病例。即使在子宫颈鳞癌和腺癌中，14-3-3sigma的表达也相对较高(13/15，87%和22/27，81%)。原位杂交结果显示，8例免疫组织化学阴性病例中有6例表达14-3-3sigma基因。因此，宫颈癌中未检测到14-3-3sigma蛋白的表达，至少部分原因可能是蛋白降解，而不是表观遗传的超甲基化。有趣的是，没有14-3-3sigma表达的癌症主要是那些缺乏HPV DNA的癌症，在本研究中没有14-3-3sigma和p16同时失活的病例。这些观察结果与14-3-3sigma或p16失活具有相当于HPV E6和E7癌蛋白表达的效应的假设一致。
14-3-3 sigma (sigma) has been a major G2/M checkpoint control gene and has demonstrated that its inactivation in various cancers occurs mostly by epigenetic hypermethylation, not by genetic change. In order to confirm 14-3-3sigma protein expression together with p16 and p53 in cervical cancers, immunohistochemistry was performed using various histological subtypes of cervical cancers and dysplasia. Strong and diffuse immunoreactivity for 14-3-3sigma was uniformly observed in all the cervical dysplasia (17/17) and squamous cell carcinomas (29/29) including human papillomavirus (HPV)-negative cases. Even in adenosquamous carcinomas and adenocarcinomas of the cervix, immunohistochemical expression of 14-3-3sigma was shown with relatively high frequency (13/15, 87% and 22/27, 81%). In the in situ hybridization study, mRNA of 14-3-3sigma was expressed in six of eight immunohistochemical-negative cases. Therefore, the undetectable expression of 14-3-3sigma protein in cervical cancers might, at least in part, be due to a proteolysis not epigenetic hypermethylation. It is of interest that cancers without 14-3-3sigma expression were predominantly those lacking HPV DNA, and that there were no cases with concomitant inactivation of 14-3-3sigma and p16 in the present study. These observations are consistent with the hypothesis that inactivation of either 14-3-3sigma or p16 has an effect equivalent to the expression of E6 and E7 oncoproteins of HPV.