Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions

Histopathology. 1999 Jul;35(1):55-64. doi: 10.1046/j.1365-2559.1999.00688.x.

Abstract

Aims: Although p27Kip1(p27) is a cyclin-dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in tumours arising in the nasal and paranasal sinus regions is still unknown.

Methods and results: Seventy-six sinonasal tumours, including 28 inverted papillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistochemically investigated, along with 46 exophytic papillomas (EPs) of upper respiratory tract and 34 samples of normal paranasal sinus epithelium. The results were also compared with expression of p21WAF1 (p21) and p53, cell proliferation assessed in terms of Ki67 labelling indices (LIs), and human papillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increase, the inverse correlation between scores for all categories being significant (r = - 0.639, P < 0. 0001). In the SCCs, p27 expression was significantly higher in keratinizing than nonkeratinizing type tumours (P < 0.05), while there was no association with p21 and p53 expression. Although HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 IPs, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident.

Conclusion: Loss of p27 expression correlates with increased cell proliferation in sinonasal tumours. Moreover, the expression appears to be associated with keratinization in SCCs of the paranasal sinus. These findings indicate that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.

Publication types

  • Comparative Study

MeSH terms

  • Blotting, Southern
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cell Cycle Proteins / metabolism*
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / metabolism
  • DNA Probes / chemistry
  • DNA, Viral / analysis
  • Down-Regulation
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Papilloma, Inverted / metabolism*
  • Papilloma, Inverted / pathology
  • Papilloma, Inverted / virology
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Paranasal Sinus Neoplasms / metabolism*
  • Paranasal Sinus Neoplasms / pathology
  • Paranasal Sinus Neoplasms / virology
  • Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins*
  • Tumor Virus Infections / metabolism*
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology

Substances

  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA Probes
  • DNA, Viral
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27