Detection of p53 protein and Ki-67 proliferation antigen in human papillomavirus (HPV)-positive and HPV-negative cervical lesions by immunohistochemical double-staining

Cytopathology. 1994 Oct;5(5):282-93. doi: 10.1111/j.1365-2303.1994.tb00432.x.


In HPV-associated genital lesions, low or absent expression of p53 has been attributed to the rapid degradation of p53 through its binding with HPV E6 protein. In this study, we examined p53 protein expression with two antibodies (CM1 polyclonal and PAb 1801 monoclonal antibodies), and Ki-67 proliferation antigen (monoclonal antibody) using an immunohistochemical (IHC) double-staining technique in 77 HPV-positive cervical lesions (HPV6, HPV11, HPV16, HPV18, HPV31, and HPV33) and in 15 HPV-negative cases. p53 protein expression was detected in 36/92 (39.1%) of the specimens. Of the p53-positive cases, 80.6% (29/36) were HPV-positive samples, including 10/23 (43.5%) of HPV16- and 3/10 (30%) of HPV18-positive biopsies. In 52.8% of the p53-positive samples, the expression was found in less than 5% of the basal cells which were also positive for Ki-67. Ki-67 proliferation marker was found in 91/92 specimens, most intensely in those infected by HPV16. p53 was more abundant in progressive or persistent lesions, but no differences were found between HPV-positive and HPV-negative samples. The positive IHC double-staining of both p53 and Ki-67 proliferation antigen in the same basal (and parabasal) cells indicates that these two normal cell-cycle proteins are being expressed while the cells are entering from the G1 to the S phase of the cell cycle. Since the latter property is only attributed to the wild-type p53 (but not to mutated p53), the p53 protein detected in HPV lesions by IHC is likely to be the wild-type p53 rather than mutated p53, and the result was also confirmed by using p53 mutant specific antibody PAb 240. Accordingly, the concept of HPV inactivating the wild-type p53 protein should be re-examined, and other mechanisms for HPV-mediated carcinogenesis should be considered.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Cell Cycle
  • Cervix Uteri / chemistry*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Cohort Studies
  • Female
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Ki-67 Antigen
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / immunology
  • Nuclear Proteins / analysis*
  • Nuclear Proteins / immunology
  • Papillomaviridae / immunology
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Paraffin Embedding
  • Precancerous Conditions / chemistry*
  • Precancerous Conditions / pathology
  • Precancerous Conditions / virology
  • Tumor Suppressor Protein p53 / analysis*
  • Tumor Suppressor Protein p53 / immunology
  • Tumor Virus Infections / metabolism*
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology


  • Antibodies, Monoclonal
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Nuclear Proteins
  • Tumor Suppressor Protein p53