Up-regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high-risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer.
Eur J Obstet Gynecol Reprod Biol
; 130(2): 223-31, 2007 Feb.
Article
in En
| MEDLINE
| ID: mdl-17098349
OBJECTIVE: Proliferating cell nuclear antigen (PCNA) is essential for DNA replication of mammalian cells and their small DNA tumour viruses. The E7 oncoprotein of high-risk human papillomavirus (HPV) is known to activate PCNA, shown to be up-regulated in CIN and cervical cancer (CC), but still incompletely studied as an intermediate endpoint marker in this disease. MATERIAL AND METHODS: As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for PCNA, and tested for HPV using PCR with three primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all SCC patients, and 67 of the CIN lesions had been monitored with serial PCR for HPV after cone treatment. RESULTS: Expression of PCNA increased in parallel with the grade of CIN, with major up-regulation upon transition to CIN3 (OR 21.77; 95%CI 6.59-71.94) (p = 0.0001). Intense PCNA expression was 100% specific indicator of CIN, with 100% PPV, but suffers from low sensitivity (34.8%) and NPV (10.8%). PCNA expression was also significantly associated to HR-HPV with OR 3.02 (95%CI 1.71-5.34) (p = 0.0001), and this association was not confounded by the histological grade (Mantel-Haenszel common OR = 2.03; 95%CI 1.06-3.89) (p = 0.033). Expression of PCNA did not predict clearance/persistence of HR-HPV after treatment of CIN, and it was not a prognostic predictor in CC in univariate or in multivariate analysis. CONCLUSIONS: Up-regulation of PCNA was closely associated with HR-HPV and progressive CIN, most feasibly explained by the abrogation of normal cell cycle control by the E7 ongogene, reverting the p21(Cip1)-mediated inhibition of PCNA. However, the fact that PCNA is also expressed in normal squamous epithelium precludes the use of this marker as a potential screening tool for CC.
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Database:
MEDLINE
Main subject:
Tumor Virus Infections
/
Carcinoma, Squamous Cell
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Biomarkers, Tumor
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Uterine Cervical Dysplasia
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Uterine Cervical Neoplasms
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Proliferating Cell Nuclear Antigen
/
Papillomavirus Infections
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Evaluation_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
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Adult
/
Aged
/
Aged80
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Female
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Humans
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Middle aged
Language:
En
Journal:
Eur J Obstet Gynecol Reprod Biol
Year:
2007
Type:
Article
Affiliation country:
Italy