title: p300 expression is related to high-risk human papillomavirus infections and severity of cervical intraepithelial neoplasia but not to viral or disease outcomes in a longitudinal setting.
abstract: To evaluate the role of the expression of the transcription factor p300 as an independent predictor of high-risk human papillomavirus (HR-HPV) infections and outcome of the cervical disease.Cervical biopsy samples taken at enrolment from 225 women of the Latin American Screening study cohort were analyzed for p300 using immunohistochemistry to assess its value as predictor of (a) cervical intraepithelial neoplasia (CIN) grade, and (b) HR-HPV at baseline, as well as (c) outcomes of HR-HPV infections, and (d) development of incident CIN as surrogate endpoints of progressive disease.There was a significant linear trend in increasing upregulation (=pattern shift) of p300 (P=0.0001) in parallel with increasing grade of CIN. When dichotomized (normal/moderately increase vs. strong-intense), upregulated p300 expression predicted CIN3+ with odds ratio=4.16 (95% confidence interval: 1.95-8.86) (P=0.0001) and CIN2+ with odds ratio=3.48 (95% confidence interval: 1.86-6.48) (P=0.0001). p300 was upregulated more often in HR-HPV+ lesions than in those remaining negative. Semiquantitative viral loads were also directly related to upregulation of p300 (P=0.036), but p300 was not a significant predictor of disease progression to either CIN1+ or CIN2+.p300 expression was upregulated in CIN lesions and related to detection and viral load of HR-HPV but not to their outcome or to incident CIN.
authors.affiliation: Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland. stina.syrjanen@utu.fi
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: Margherita
authors.initials: M
authors.lastname: Branca
authors.forename: Mojca
authors.initials: M
authors.lastname: Erzen
authors.forename: Luciano
authors.initials: L
authors.lastname: Serpa-Hammes
authors.forename: Jean
authors.initials: J
authors.lastname: Matos
authors.forename: Fernanda
authors.initials: F
authors.lastname: Arlindo
authors.forename: Marina
authors.initials: M
authors.lastname: Sakamoto-Maeda
authors.forename: Silvano
authors.initials: S
authors.lastname: Costa
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001706:Biopsy; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human