Cell-cycle analysis and apoptosis-associated proteins in cervical lesions of Brazilian women

Anticancer Res. 2014 Jun;34(6):2789-96.

Abstract

Aim: The aim of the present study was to detect the relative expressions of p53, p21(Waf1/Cip1), p27(Kip1) Bcl-2 and cleaved caspase-3 in cervical lesion samples from Brazilian women by immunohistochemistry.

Materials and methods: A total of 230 cervical biopsies in paraffin-embedded blocks were studied: 43 were invasive squamous cell carcinomas (SCC), 52 carcinomas in situ/cervical intraepithelial neoplasias III (CIN III), 54 cervical intraepithelial neoplasias II (CIN II), 51 cervical intraepithelial neoplasias I (CIN I) and 30 non-neoplastic lesions (NN) with benign cellular changes.

Results: Significant differences were observed in the p53 expression between the different groups: NN and CIN I (p=0.010); NN and CIN II (p<0.00001); CIN II and CIN III (p=0.02); CIN II and CIS (p=0.0220); CIN II and CEC (p=0.010). Regarding p21(WAF1/Cip1), significant differences were observed between NN and CEC (p=0.001); CIN I and CEC (p=0.001); CIN II and CIN III (p=0,001); CIN II and CIS (p=0.0004) and CIN II and CEC (p<0.0001). For p27(Kip1), significant differences were observed between NN and CIN I (p<0.00001); NN and CIN II (p<0.00001); NN and CIS (p=0.038); CIN I and CIN III (p=0.001); CIN I and CIS (p=0.009); CIN I and CEC (p=0.0001); CIN II and CIN III (p=0.0003); CIN II and CIS (p=0.002); CIN II and CEC (p< 0.00001). Bcl-2 and caspase-3 did not show remarkable differences between groups.

Conclusion: p53, p21(WAF1/CIP1), p27(KIP1) appear to be involved in the course of carcinogenesis. Rare expression of Bcl-2 and cleaved caspase-3 suggests that these proteins probably do not participate in cervical apoptosis.

Keywords: Cervical cancer; apoptosis; bcl-2; caspase-3; p21WAF1/Cip1; p27Kip1; p53.

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Brazil
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • CDKN1A protein, human
  • CDKN1B protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27
  • Caspase 3