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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

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Detalhes bibliográficos
Resumo: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.
Autores principais:Syrjänen, Stina
Outros Autores:Naud, Paulo; Sarian, Luis; Derchain, Sophie; Roteli-Martins, Cecilia; Longatto, Adhemar; Tatti, Silvio; Branca, Margerita; Erzen, Mojca; Hammes, Luciano S.; Costa, Silvano; Syrjänen, Kari
Assunto:Biomarkers, Tumor Cell Nucleus Cervical Intraepithelial Neoplasia DNA, Viral Disease Progression Female Humans Immunohistochemistry Papillomaviridae Papillomavirus Infections Plasminogen Activator Inhibitor Type 2 Predictive Value of Tests Up-Regulation Uterine Cervical Neoplasms Viral Load High-risk human papillomavirus HPV PAI-2 Serpin-B2 Cytoplasmic Nuclear CIN Baseline Viral outcomes Longitudinal predictive values Surrogate end points
Ano:2009
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo: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.