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

被引:63
作者
Branca, M
Ciotti, M
Santini, D
Di Bonito, L
Benedetto, A
Giorgi, C
Paba, P
Favalli, C
Costa, S
Agarossi, A
Alderisio, M
Syrjänen, K
机构
[1] Ist Super Sanita, Ctr Nazl Epidemiol Sorveglianza & Promoz Salute, Unita Citoistopatol, I-00161 Rome, Italy
[2] Univ Hosp Policlin Tor Vergata, Lab Clin Microbiol & Virol, Rome, Italy
[3] Azienda Osped S Orsola Malpighi, Dipertimento Ginecol & Ostetr, Bologna, Italy
[4] UCO, Osped Maggiore, Trieste, Italy
[5] ISS, Dept Infect Parasit & Immunomediated Dis, Rome, Italy
关键词
ERK1; MAPK pathway; human papillomavirus; HPV E5 protein; CIN; cervical intraepithelial neoplasia; cervical cancer; prognosis; virus clearance;
D O I
10.1309/VQXFT880JXC7QD2W
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
We subjected 302 archival samples (150 squamous cell carcinomas [SCCs] and 152 cervical intraepithelial neoplasia [CIN] lesions) to imnumohistochemical staining with extracellular signal-regulated kinase-1 (ERK1) antibody and human papillomavirus (HPV) testing with 3 printer sets. Follow-tip 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% Cl, 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 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
引用
收藏
页码:902 / 911
页数:10
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