p16INK4A Expression Is Related to Grade of CIN and High-risk Human Papillomavirus but Does not Predict Virus Clearance After Conization or Disease Outcome

Autor: Margherita Branca, L. Di Bonito, Cartesio Favalli, M Alderisio, A Agarossi, S. Costa, K Syrjänen, Arrigo Benedetto, P Paba, Marco Ciotti, Donatella Santini, Colomba Giorgi
Rok vydání: 2004
Předmět:
Adult
Human papillomavirus
Pathology
medicine.medical_specialty
Adolescent
Conization
Uterine Cervical Neoplasms
Cervical intraepithelial neoplasia
Polymerase Chain Reaction
Sensitivity and Specificity
Pathology and Forensic Medicine
Virus clearance-Conization
p16INK4a
Prognostic marker
Biomarkers
Tumor
medicine
Humans
CIN
Papillomaviridae
Stage (cooking)
neoplasms
Cervical cancer
Cyclin-Dependent Kinase Inhibitor p16
Survival analysis
Univariate analysis
biology
business.industry
Papillomavirus Infections
virus diseases
Obstetrics and Gynecology
Middle Aged
Settore MED/07 - Microbiologia e Microbiologia Clinica
Prognosis
Uterine Cervical Dysplasia
biology.organism_classification
medicine.disease
Immunohistochemistry
Survival Analysis
female genital diseases and pregnancy complications
Staining
Female
business
Zdroj: International Journal of Gynecological Pathology. 23:354-365
ISSN: 0277-1691
DOI: 10.1097/01.pgp.0000139639.79105.40
Popis: The role of p16(INK4A) as a marker of HR-HPV and in the diagnosis of CIN has been well established, but its predictive value in the clearance of the virus after CIN treatment and its use as a prognostic marker of cervical cancer has not been studied. A series of 302 archival samples, including 150 squamous cell carcinomas (SCCs) and 152 CIN lesions, were subjected to immunohistochemical staining for p16(INK4A) and HPV testing using PCR with three primer sets (MY09/11, GP5/GP6, SPF). Follow-up data were available of 88 SCC patients, and 67 of the CIN lesions had been followed-up with serial PCR after conization. HR-HPV types were closely associated with CIN (OR 19.12; 95%CI 2.31-157.81) and SCC (OR 27.25; 95%CI 3.28-226.09). There was a significant linear relationship between the lesion grade and intensity of p16(INK4A) staining (p = 0.0001). The expression of p16(INK4A) was also closely related to HR-HPV (p = 0.0001). p16(INK4A) staining was a 100% specific indicator of CIN, with 100% PPV, and showed 83.5% sensitivity and 80.1% PPV in detecting HR-HPV. However, p16(INK4A) staining did not predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, despite a slightly more favorable survival in women with strong/intense p16(INK4A) staining in univariate analysis, p16(INK4A) expression was not an independent prognostic predictor in multivariate survival (Cox) analysis. After adjustment for p16(INK4A) staining, HR-HPV, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and age, only the last two were significant prognostic predictors (p = 0.0001 and p = 0.003, respectively). The present data confirm the role of p16(INK4A) as a highly specific marker of CIN and HR-HPV type, but expression of this protein does not seem to be of any prognostic value in cervical cancer or in predicting the clearance of HR-HPV after treatment of CIN. We speculate that different subgroups of cervical cancer are characterized by aberrant p16(INK4A)/cyclin D/Rb pathways that are due to different mechanisms that can be mutually exclusive.
Databáze: OpenAIRE
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