title: Up-regulation of plasminogen activator inhibitor-2 is associated with high-risk HPV and grade of cervical lesion at baseline but does not predict outcomes of high-risk HPV infections or incident CIN.
abstract: Protease inhibitor serpin-B2 (plasminogen activator inhibitor-2 [PAI-2]) protects pRb from degradation in human papillomavirus (HPV)-18+ HeLa cells. Our objective was to assess whether the pRb-mediated HPV-suppressive effect of PAI-2 in cancer cell lines has implications in the outcome of HPV infections. Cervical biopsy specimens from 225 women were analyzed for PAI-2 expression to assess its value as a predictor of cervical intraepithelial neoplasia (CIN) grade, high-risk (HR) HPV at baseline, outcomes of HR-HPV infections, and the development of incident CIN. PAI-2 expression increased in parallel with lesion grade. Nuclear PAI-2 expression was significantly related to HR-HPV detection and had a linear relationship with HR-HPV load. PAI-2 expression was of no value in predicting the outcomes of HR-HPV infections. The same was true for PAI-2 as a predictor of surrogate end points (incident CIN 1+, CIN 2+) of progressive disease. PAI-2 expression is up-regulated on transition from CIN 2 to CIN 3. The HR-HPV suppressive effects of PAI-2 were not related to more favorable outcomes of HR-HPV infections or lower risk of disease progression to CIN.
authors.affiliation: Department of Oral Pathology, Institute of Dentistry, University of Turku, 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: Adhemar
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: D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism*; D011237:Predictive Value of Tests; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D017396:Plasminogen Activator Inhibitor 2