Co-expression of p53 and Bcl-2 proteins in human papillomavirus-induced premalignant lesions of the uterine cervix: correlation with progression to malignancy

Tumour Biol. 2009;30(5-6):276-85. doi: 10.1159/000259911. Epub 2009 Nov 20.

Abstract

Objective(s): To analyze aberrant expression of the apoptotic protein p53 and the anti-apoptotic protein Bcl-2 in premalignant lesions of the uterine cervix induced by human papillomavirus (HPV) infection and its significance for early diagnosis of cervical cancer.

Materials and methods: Cytological adequate smears (n = 382) from various grades of squamous intraepithelial lesions (SILs; n = 142), 'atypical squamous cells of unknown significance' (ASCUS; n = 128) and normal tissue (n = 112) were investigated immunocytochemically for aberrant expression of p53 and Bcl-2 proteins using the streptavidin-biotin-peroxidase method; HPV status was analyzed in cervical smears using general and type-specific primers.

Results: HPV-DNA of any type was detected in 25.7% (98/382) of cases. HPV16 was seen in 58.2% (57/98), HPV18 in 20.4% (20/98) and other HPV types in 21.4% (21/98). Abnormal nuclear expression of p53 protein and cytoplasmic expression of Bcl-2 protein were noted in cervical dysplasia and an association with the presence of HPV16/HPV18 was noted. The intensity of immunoreactivity for p53 and Bcl-2 proteins varied between different cytological grades of cervical smears. Follow-up data revealed that cases with high-risk HPV and co-induced expression of apoptosis-regulatory proteins presented a trend to progressive disease.

Conclusions: The detection of both p53 and Bcl-2 proteins in cervical smears can be used as independent diagnostic marker for early-stage HPV-associated cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus / classification
  • Alphapapillomavirus / genetics
  • Alphapapillomavirus / physiology
  • Biomarkers, Tumor / biosynthesis
  • Cytodiagnosis
  • DNA, Viral / genetics
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Host-Pathogen Interactions
  • Humans
  • Immunohistochemistry
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears

Substances

  • Biomarkers, Tumor
  • DNA, Viral
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53