Evaluation of Elafin Immunohistochemical Expression as Marker of Cervical Cancer Severity

Acta Cytol. 2021;65(2):165-174. doi: 10.1159/000512010. Epub 2020 Dec 3.

Abstract

Introduction: The main risk factor for the development of cervical cancer (CC) is persistent infection by human papillomavirus (HPV) oncogenic types. In order to persist, HPV exhibits a plethora of immune evasion mechanisms. PI3/Elafin (Peptidase Inhibitor 3) is an endogenous serine protease inhibitor involved in epithelial protection against pathogens. PI3/Elafin's role in CC is still poorly understood.

Materials and methods: In the present study, we addressed PI3/Elafin protein detection in 123 CC samples by immunohistochemistry and mRNA expression in several datasets available at Gene Expression Omnibus and The Cancer Genome Atlas platforms.

Results: We observed that PI3/Elafin is consistently downregulated in CC samples when compared to normal tissue. Most of PI3/Elafin-positive samples exhibited this protein at the plasma membrane. Besides, high PI3/Elafin expression at the cellular membrane was more frequent in in situ stages I + II than in invasive cervical tumor stages III + IV. This indicates that PI3/Elafin expression is gradually lost during the CC progression. Of note, advanced stages of CC were more frequently associated with a more intense PI3/Elafin reaction in the nuclei and cytoplasm.

Conclusion: Our results suggest that PI3/Elafin levels and subcellular localization may be used as a biomarker for CC severity.

Keywords: Cervical carcinoma; Elafin; HPV-induced cancer; Tumorigenesis.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma / chemistry*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Databases, Genetic
  • Elafin / analysis*
  • Elafin / genetics
  • Female
  • Humans
  • Immunohistochemistry*
  • Neoplasm Grading
  • Neoplasm Staging
  • Predictive Value of Tests
  • Retrospective Studies
  • Severity of Illness Index
  • Up-Regulation
  • Uterine Cervical Neoplasms / chemistry*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Elafin
  • PI3 protein, human