title: Up-regulation of 14-3-3sigma (Stratifin) is associated with high-grade CIN and high-risk human papillomavirus (HPV) at baseline but does not predict outcomes of HR-HPV infections or incident CIN in the LAMS study.
abstract: To assess whether the potentially high-risk (HR) human papillomavirus (HPV)-related up-regulation of 14-3-3sigma (stratifin) has implications in the outcome of HPV infections or cervical intraepithelial neoplasia (CIN) lesions, cervical biopsy specimens from 225 women in the Latin American Screening Study were analyzed for 14-3-3sigma expression using immunohistochemical analysis. We assessed its associations with CIN grade and HR HPV at baseline and value in predicting outcomes of HR-HPV infections and the development of incident CIN 1+ and CIN 2+. Expression of 14-3-3sigma increased in parallel with the lesion grade. Up-regulation was also significantly related to HR-HPV detection (P = .004; odds ratio, 2.71; 95% confidence interval, 1.37-5.35) and showed a linear relationship to HR-HPV loads (P = .003). 14-3-3sigma expression was of no value in predicting the outcomes (incident, persistent, clearance) of HR-HPV infections or incident CIN 1+ and CIN 2+. 14-3-3sigma is not inactivated in cervical carcinoma and CIN but is up-regulated on transition from CIN 2 to CIN 3. Its normal functions in controlling G(1)/S and G(2)/M checkpoints are being bypassed by HR HPV.
authors.affiliation: Department of Oncology & Radiotherapy, Turku University Hospital, Turku, Finland.
authors.forename: Stina
authors.initials: S
authors.lastname: Syrjänen
authors.forename: Paulo
authors.initials: P
authors.lastname: Naud
authors.forename: Luis
authors.initials: L
authors.lastname: Sarian
authors.forename: Sophie
authors.initials: S
authors.lastname: Derchain
authors.forename: Cecilia
authors.initials: C
authors.lastname: Roteli-Martins
authors.forename: Adhernar
authors.initials: A
authors.lastname: Longatto-Filho
authors.forename: Silvio
authors.initials: S
authors.lastname: Tatti
authors.forename: Margerita
authors.initials: M
authors.lastname: Branca
authors.forename: Mojca
authors.initials: M
authors.lastname: Erzen
authors.forename: Luciano S
authors.initials: LS
authors.lastname: Hammes
authors.forename: Silvano
authors.initials: S
authors.lastname: Costa
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
mesh_terms: D048948:14-3-3 Proteins; D052685:Alphapapillomavirus; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D005092:Exonucleases / Q000235:genetics*; D005095:Exoribonucleases; D005260:Female; D006801:Humans; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics*; D016896:Treatment Outcome; D015854:Up-Regulation; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human