Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers.
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.
Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Gunma, Japan. sanot@med.gunma-u.ac.jp
Takaaki
T
Sano
Hanako
H
Shimooka
Peng
P
Weixa
Atsuki
A
Segawa
Zhang
Z
Jian
Atsushi
A
Motegi
Hiroko
H
Nakayama
Tetsunari
T
Oyama
Takashi
T
Nakajima
D048948:14-3-3 Proteins; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D018196:Carcinoma, Adenosquamous / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human