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Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers


Takaaki Sano, MD, Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Email:


14-3-3 sigma (σ) 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 14-3-3σ 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 14-3-3σ 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 14-3-3σ was shown with relatively high frequency (13/15, 87% and 22/27, 81%). In the in situ hybridization study, mRNA of 14-3-3σ was expressed in six of eight immunohistochemical-negative cases. Therefore, the undetectable expression of 14-3-3σ protein in cervical cancers might, at least in part, be due to a proteolysis not epigenetic hypermethylation. It is of interest that cancers without 14-3-3σ expression were predominantly those lacking HPV DNA, and that there were no cases with concomitant inactivation of 14-3-3σ and p16 in the present study. These observations are consistent with the hypothesis that inactivation of either 14-3-3σ or p16 has an effect equivalent to the expression of E6 and E7 oncoproteins of HPV.