Expression of 14-3-3sigma in cervical squamous cell carcinomas: relationship with clinical outcome.
14-3-3 sigma (sigma) sequesters the cdc2-cyclin B1 complex in the cytoplasm resulting in G2 arrest. Inactivation and reduced expression of 14-3-3sigma have been reported in a varity of cancers. In the present study, we investigated the expression of 14-3-3sigma in a series of 297 cervical squamous cell carcinoma (SCC) to clarify the prognostic value. Using immunohistochemical methods we found high levels of 14-3-3sigma protein in cytoplasm of 143 (48.1%), in nucleus of 113 (38.0%) and in both cytoplasm and nucleus of 147 (49.5%) cases, whereas, low levels were present in cytoplasm of 154 (51.9%), in nucleus of 184 (62.0%) and in both cytoplasm and nucleus of 150 (50.5%) cases. Levels of 14-3-3sigma mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and 14-3-3sigma protein were not significant associated. 14-3-3sigma expression in cytoplasm, nuclear and cytoplasm/nuclear were not significantly correlated to disease-specific survival or disease-free survival. In conclusion, reduced expression of 14-3-3sigma protein in the cytoplasm and shuttle of 14-3-3sigma protein into the nucleus in a relatively high number of cases indicate that 14-3-3sigma may be important in the carcinogenesis of cervical SCCs by two different mechanisms; reduction and nuclear translocation of 14-3-3sigma protein. Furthermore, the non-significant correlation between expression levels of 14-3-3sigma mRNA and protein support a post-transcriptional regulation in cervical SCCs. The protein has no prognostic value in cervical cancers.
Holm
Ruth
R
Division of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ruth.holm@radiumhospitalet.no
Ali
Tayeba
T
Svendsrud
Debbie H
DH
Nesland
Jahn M
JM
Kristensen
Gunnar B
GB
Lyng
Heidi
H
D048948:14-3-3 Proteins; D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D018572:Disease-Free Survival; D005092:Exonucleases / Q000032:analysis* / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human