Claudin-1 as a Biomarker of Cervical Cytology and Histology

Pathol Oncol Res. 2016 Jan;22(1):179-88. doi: 10.1007/s12253-015-9990-z.

Abstract

Several immunochemistry tests are used for triaging human papilloma virus (HPV) and cytology positive cases in cervical cancer screening and as an adjunct test to diagnose cervical cancer. Claudin-1 (CLDN1) protein is a major component of the tight junction, shown to have altered expression in cervical cancer. In this study, value of CLDN1 was analysed as a screening and triage immunochemistry test compared to cytology and HPV testing. A population of 352 women attending colposcopic referral visits resulting in cervical conisation and a second population of 150 women attending routine gynaecological visits with negative cervical cytology were enrolled in a multi-centre clinical study in Hungary. Cytology and HPV (Genoid Full Spectrum HPVAmplification and Detection System) testing were carried out along with immunocytochemistry for CLDN1, and as a reference, using CINtec p16 Cytology Kit. Three different evaluation protocols were used which assessed immunostaining characteristics with or without cytological readings. High correlation observable between p16INK4a and CLDN1 established CLDN1 as a competing marker in cervical cancer. Concordance of CLDN1 immunostaining of cervical intraepithelial neoplasia 2 and above (CIN2+) positives was 84.0 % (73.8–89.3); concordance of CIN2+ negatives was 69.0 % (59.6–75.8). In conclusion, CLDN1 has similar diagnostic potential as p16INK4a, our results established it as a histological and cytological biomarker with the potential to improve the clinical performance of cervical cytology and histology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cervical Intraepithelial Neoplasia / metabolism
  • Cervical Intraepithelial Neoplasia / pathology*
  • Cervical Intraepithelial Neoplasia / virology
  • Claudin-1 / metabolism*
  • Colposcopy
  • Cytodiagnosis*
  • Early Detection of Cancer
  • Female
  • Follow-Up Studies
  • Humans
  • Hungary
  • Immunoenzyme Techniques
  • Neoplasm Grading
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / pathology*
  • Neoplasms, Squamous Cell / virology
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Prognosis
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • Biomarkers, Tumor
  • CLDN1 protein, human
  • Claudin-1