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

• Published in: American journal of clinical pathology Vol. 122; no. 6; pp. 902 - 911
• Main Authors: BRANCA, Margherita, CIOTTI, Marco, ALDERISIO, Mauro, SYRJÄNEN, Kari, SANTINI, Donatella, DI BONITO, Luigi, BENEDETTO, Arrigo, GIORGI, Colomba, PABA, Pierpaolo, FAVALLI, Carterio, COSTA, Silvano, AGAROSSI, Alberto
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Society of Clinical Pathologists 01.12.2004
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma in Situ - enzymology; Carcinoma in Situ - pathology; Carcinoma in Situ - virology; Enzyme Activation - physiology; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Middle Aged; Mitogen-Activated Protein Kinase 3 - metabolism; Papillomaviridae; Papillomavirus Infections - enzymology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction; Prognosis; Tumor Virus Infections - enzymology; Tumors; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; High risk; HPV E5 protein; Prognosis; Extracellular signal-regulated protein kinase; Activation; Papovaviridae; Clearance; Papillomavirus; Human papillomavirus; ERK1; Cervical dysplasia; Cervical intraepithelial neoplasia; MAPK pathway; Premalignant lesion; Enzyme; Mitogen-activated protein kinase; CIN; Malignant tumor; Protein; Female genital diseases; Virus; Anatomic pathology; Uterine cervix diseases; Cervical cancer; Virus clearance
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1309/VQXFT880JXC7QD2W

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.