title: Activation of the ERK/MAP kinase pathway in cervical intraepithelial neoplasia is related to grade of the lesion but not to high-risk human papillomavirus, virus clearance, or prognosis in cervical cancer.
abstract: We subjected 302 archival samples (150 squamous cell carcinomas [SCCs] and 152 cervical intraepithelial neoplasia [CIN] lesions) to immunohistochemical staining with extracellular signal-regulated kinase-1 (ERK1) antibody and human papillomavirus (HPV) testing with 3 primer sets. Follow-up data were available for all SCC cases and 67 CIN cases. High-risk (HR) HPV types were associated with CIN (odds ratio [OR], 19.12; 95% confidence interval [CI], 2.31-157.81) and SCC (OR, 27.25; 95% CI, 3.28226.09). There was a significant linear relationship between lesion grade and ERK1 staining intensity (P = .0001). ERK1 staining was a 100% specific indicator of CIN, with a 100% positive predictive value, but a poor predictor of HR HPV. ERK1 expression did not predict clearance or persistence of HR HPV after CIN treatment. ERK1 staining did not significantly predict survival in cervical cancer in univariate (P = .915) or multivariate analysis. After adjustment for HR HPV, stage, age, and tumor grade in the Cox regression model, only stage (P = .0001) and age (P = .002) remained independent prognostic factors. ERK1 expression seems to be an early marker of cervical carcinogenesis. ERK1 overexpression is not a specific marker of HR-HPV in CIN and cervical cancer, nor does it predict virus clearance after CIN treatment or disease outcome in cervical cancer.
authors.affiliation: Unità Citoistopatologia, Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità, Rome.
authors.forename: Margherita
authors.initials: M
authors.lastname: Branca
authors.forename: Marco
authors.initials: M
authors.lastname: Ciotti
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini
authors.forename: Luigi Di
authors.initials: LD
authors.lastname: Bonito
authors.forename: Arrigo
authors.initials: A
authors.lastname: Benedetto
authors.forename: Colomba
authors.initials: C
authors.lastname: Giorgi
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Paba
authors.forename: Carterio
authors.initials: C
authors.lastname: Favalli
authors.forename: Silvano
authors.initials: S
authors.lastname: Costa
authors.forename: Alberto
authors.initials: A
authors.lastname: Agarossi
authors.forename: Mauro
authors.initials: M
authors.lastname: Alderisio
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014412:Tumor Virus Infections / Q000201:enzymology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3