Evaluation of MCM-2 expression in TMA cervical specimens

PLoS One. 2012;7(4):e32936. doi: 10.1371/journal.pone.0032936. Epub 2012 Apr 6.

Abstract

Background: Minichromosome maintenance proteins (MCM) are highly expressed in actively replicating cells. The need for biological markers for cervical carcinoma and its precursor lesions is emerging. Our main aim was to determine the immunohistochemical expression of MCM-2 in HIV-positive and -negative dysplastic cervical specimens.

Methods: Immunohistochemical analysis of MCM-2 was performed in a total of 352 cervical TMA specimens of normal control, low-grade CIN, high-grade CIN and invasive tumor. 38 specimens were from HIV-positive women. A receiver operating characteristic (ROC) curve was constructed to determine the best cutoff to diagnose high-grade CIN and invasive cervical cancer.

Results: In the progression from normal epithelium to high-grade CIN and invasive tumor we found significant differences in the MCM-2 expression (p<0.05). Based on the ROC curve of 80% with an area under the curve (AUC) of 0.78, expression of MCM-2 to diagnose high-grade CIN and invasive tumor resulted in sensitivity of 81%, specificity of 66%, a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 57%. HIV-positive cervices revealed a decreasing expression of MCM-2 in both LGCIN and HGCIN compared with HIV-negative specimens (p<0.0001).

Conclusions: The present study suggests that immunohistochemical MCM-2 may not be a promising biomarker for diagnosing high-grade CIN and invasive cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Coinfection
  • Epithelium / metabolism
  • Epithelium / pathology
  • Epithelium / virology
  • Female
  • Gene Expression
  • HIV / physiology
  • HIV Infections / metabolism
  • HIV Infections / virology
  • Humans
  • Immunohistochemistry
  • Minichromosome Maintenance Complex Component 2
  • Neoplasm Grading
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Papillomaviridae / physiology
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Predictive Value of Tests
  • ROC Curve
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Nuclear Proteins
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2