Survivin as a marker of cervical intraepithelial neoplasia and high-risk human papillomavirus and a predictor of virus clearance and prognosis in cervical cancer.
We analyzed survivin as a marker of cervical intraepithelial neoplasia (CIN) and high-risk human papillomavirus (HR-HPV) and a predictor of HPV clearance and disease outcome in cervical cancer in 302 samples (squamous cell carcinomas [SCCs], 150; CIN lesions, 152) by immunohistochemical staining with survivin antibody and HPV testing using polymerase chain reaction. HR-HPV types were associated closely with CIN and SCC. There was a significant linear relationship between grade and intensity of survivin expression (P = .0001). Survivin overexpression also was associated strongly with HR-HPV type (P = .0001). Multivariate regression analysis revealed survivin and p16(INK4a) as equally strong independent predictors of HR-HPV. Deregulated survivin expression did not predict clearance or persistence of HR-HPV after treatment of CIN or survival in cervical cancer in univariate (P = .417) or multivariate analysis. After adjustment for HR-HPV, stage, age, and tumor grade in the Cox regression model, only stage (P = .0001) and age (P = .0001) remained independent prognostic predictors. Survivin seems to be an early marker of cervical carcinogenesis. Up-regulated survivin expression was an independent predictor of HR-HPV in cervical lesions, most plausibly explained by its normal transcriptional repression by wild-type p53 being eliminated by HR-HPV E6 oncoprotein.
Branca
Margherita
M
Unità Citoistopatologia, Centro Nazionale di, Epidemiologia, Sorveglianza e Promozione della Salute, Rome, Italy.
Giorgi
Colomba
C
Santini
Donatella
D
Di Bonito
Luigi
L
Ciotti
Marco
M
Costa
Silvano
S
Benedetto
Arrigo
A
Casolati
Elena A
EA
Favalli
Cartesio
C
Paba
Pierluigi
P
Di Bonito
Paola
P
Mariani
Luciano
L
Syrjänen
Stina
S
Bonifacio
Donatella
D
Accardi
Luisa
L
Zanconati
Francesca
F
Syrjänen
Kari
K
D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000401:mortality / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D000077022:Survivin; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000401:mortality / Q000473:pathology / Q000821:virology*
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin