Evaluation of expression of apoptosis-related proteins and their correlation with HPV, telomerase activity, and apoptotic index in cervical cancer

Pathobiology. 2004;71(6):314-22. doi: 10.1159/000081727.

Abstract

Objective: The aim of this study was to examine the expression of apoptosis-related proteins in cervical cancer, and investigate their correlation with the apoptotic index (AI), telomerase activity, human papilloma virus (HPV) infection and clinicopathological characteristics.

Methods: Fifty cervical cancer samples and 20 normal cervical tissues were assessed for the protein expression of survivin, Bcl-2, Cox-2, p53 and p73 by immunohistochemistry. HPV DNA was detected by PCR, telomerase activity by PCR-ELISA, and AI by TUNEL assay.

Results: 46/50 cervical tumors (92%) showed an increased telomerase activity as compared to 3/20 (15%) controls. 45/50 (90%) cervical tumors were positive for HPV, of which 30 were HPV-16 positive and 5 were HPV-18 positive. 24/50 (48%) tumors were positive for survivin, 14 (28%) for Bcl-2, 13 (26%) for Cox-2, 19/45 (42%) for p73, 10/45 (24%) for p53. Telomerase activity was highest in tumors with the poorest grade. A positive correlation was seen between survivin and Bcl-2, survivin and tumor stage, Bcl-2 and Cox-2, p73 and p53 and p73 and the AI. Despite the overexpression of various antiapoptotic proteins, no significant difference was observed in the AI between tumors and controls.

Conclusions: Since deregulation of the apoptotic pathway appears to occur in cervical cancer, some apoptosis-related proteins could be assessed as potential markers for progression/prognosis in cervical cancer. Additionally, newer proteins such as p73 may play a compensatory role for the nonfunctional proteins such as p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / physiology*
  • Biomarkers, Tumor / analysis*
  • Cyclooxygenase 2
  • DNA-Binding Proteins / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins / biosynthesis
  • Middle Aged
  • Neoplasm Proteins
  • Nuclear Proteins / biosynthesis
  • Papillomaviridae / genetics
  • Papillomavirus Infections / complications*
  • Polymerase Chain Reaction
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Survivin
  • Telomerase / metabolism*
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Proteins
  • Tumor Virus Infections / complications*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / virology

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Telomerase