title: Up-regulation of lipocalin 2 is associated with high-risk human papillomavirus and grade of cervical lesion at baseline but does not predict outcomes of infections or incident cervical intraepithelial neoplasia.
abstract: Our objective was to assess whether neutrophil gelatinase-associated lipocalin (NGAL)/lipocalin 2 (LCN2) expression in cervical human papillomavirus (HPV) lesions has implications on the outcome of HPV infections or disease progression. Cervical biopsy specimens from 225 women in the Latin American Screening study were analyzed for NGAL/LCN2 expression using immunohistochemical analysis, to assess associations with cervical intraepithelial neoplasia (CIN) grade, high-risk HPV, and in predicting outcomes of high-risk (HR)-HPV infections. Expression of NGAL/LCN2 increased with lesion grade (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.53-9.71; P = .001). Up-regulation was also related to HR-HPV detection (OR, 2.21; 95% CI, 1.15-4.24; P = .016) and showed a linear relationship to HR-HPV load (P = .002). NGAL/LCN2 expression was of no value in predicting the outcomes of HR-HPV infections or the surrogate end points (incident CIN 1+ and CIN 2+) of progressive disease. Because the SV40 large T antigen is a powerful up-regulator of this lipocalin, up-regulation of NGAL/LCN2 in CIN is probably induced by HR-HPV E6 oncoprotein, most likely by eliminating its normal transcription repression exerted by wild-type p53.
authors.affiliation: Department of Oral Pathology, Institute of Dentistry, University of 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: 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: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007843:Latin America; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008403:Mass Screening / Q000379:methods; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; D004279:DNA, Viral; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins