Journal Article

γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

Pappas, Asimakis, Pouliakis, Abraham, Karakitsos, Petros, Kelesidis, Theodore, Kefala, Maria, Kottaridi, Christine, Sioulas, Vasileios, Gouloumi, Alina-Roxani, Panayiotides, Ioannis, Tsiodras, Sotirios, Chrelias, Charalambos, Leventakos, Konstantinos, Spathis, Aris

2017

Overview

γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenocarcinoma / Adenocarcinoma - chemistry / Adenocarcinoma - diagnosis / Adenocarcinoma - virology / Adolescent / Adult / Aged / Aged, 80 and over / Biology and Life Sciences / Biomarkers / Biomarkers, Tumor - analysis / Biomarkers, Tumor - biosynthesis / Breakage / Cancer / Carcinoma, Squamous Cell - chemistry / Carcinoma, Squamous Cell - diagnosis / Carcinoma, Squamous Cell - virology / Cell cycle / Cellular biology / Cervical cancer / Cervical carcinoma / Cervix / Cervix Uteri - metabolism / Cervix Uteri - virology / Deoxyribonucleic acid / Diagnosis, Differential / DNA / DNA damage / DNA repair / Epithelial Cells - chemistry / Epithelial Cells - virology / Epithelium / Female / Gene expression / Gynecology / Histones - analysis / Histones - biosynthesis / Human papillomavirus / Human Papillomavirus DNA Tests / Humans / Internal medicine / Kinases / Lesions / Medicine / Medicine and Health Sciences / Middle Aged / Neoplasm Grading / Neoplasm Proteins - analysis / Neoplasm Proteins - biosynthesis / Obstetrics / Papillomaviridae - isolation & purification / Papillomaviridae - physiology / Papillomavirus Infections - metabolism / Papillomavirus Infections - virology / Pathogenesis / Pathology / Phosphorylation / Proteins / Research and Analysis Methods / Risk / Senescence / Squamous cell carcinoma / Squamous Intraepithelial Lesions of the Cervix - diagnosis / Squamous Intraepithelial Lesions of the Cervix - metabolism / Squamous Intraepithelial Lesions of the Cervix - virology / Studies / Tumorigenesis / Uterine Cervical Dysplasia - chemistry / Uterine Cervical Dysplasia - diagnosis / Uterine Cervical Dysplasia - virology / Uterine Cervical Neoplasms - chemistry / Uterine Cervical Neoplasms - diagnosis / Uterine Cervical Neoplasms - virology / Virus Activation / Virus Latency / Viruses / Young Adult