title: γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL.
abstract: BACKGROUND
  γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 2nd Department of Pathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|4th Department of Internal Medicine, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Leventakos
authors.affiliation: 4th Department of Internal Medicine, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Sotirios
authors.identifier: http://orcid.org/0000-0002-0463-4321
authors.initials: S
authors.lastname: Tsiodras
authors.affiliation: 4th Department of Internal Medicine, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: 2nd Department of Pathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kefala
authors.affiliation: Department of Cytopathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Christine
authors.initials: C
authors.lastname: Kottaridi
authors.affiliation: Department of Cytopathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Aris
authors.initials: A
authors.lastname: Spathis
authors.affiliation: 2nd Department of Pathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Alina-Roxani
authors.initials: AR
authors.lastname: Gouloumi
authors.affiliation: Department of Cytopathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Abraham
authors.initials: A
authors.lastname: Pouliakis
authors.affiliation: 3rd Department of Obstetrics and Gynecology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Asimakis
authors.initials: A
authors.lastname: Pappas
authors.affiliation: 3rd Department of Obstetrics and Gynecology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Sioulas
authors.affiliation: 3rd Department of Obstetrics and Gynecology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Chrelias
authors.affiliation: Department of Cytopathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Karakitsos
authors.affiliation: 2nd Department of Pathology, University Hospital "Attikon", School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panayiotides
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology; D003937:Diagnosis, Differential; D004847:Epithelial Cells / Q000737:chemistry / Q000821:virology; D005260:Female; D006657:Histones / Q000032:analysis* / Q000096:biosynthesis; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis; D027383:Papillomaviridae / Q000302:isolation & purification / Q000502:physiology; D030361:Papillomavirus Infections / Q000378:metabolism / Q000821:virology; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000175:diagnosis* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones; D009363:Neoplasm Proteins