A panel of p16(INK4A), MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma

Int J Cancer. 2008 Dec 15;123(12):2767-73. doi: 10.1002/ijc.23857.

Abstract

Two pathways leading to vulvar squamous cell carcinoma (SCC) exist. The expression of proliferation- and cell-cycle-related biomarkers and the presence of high-risk (hr) HPV might be helpful to distinguish the premalignancies in both pathways. Seventy-five differentiated vulvar intra-epithelial neoplasia (VIN)-lesions with adjacent SCC and 45 usual VIN-lesions (32 solitary and 13 with adjacent SCC) were selected, and tested for hr-HPV DNA, using a broad-spectrum HPV detection/genotyping assay (SPF(10)-LiPA), and the immunohistochemical expression of MIB1, p16(INK4A) and p53. All differentiated VIN-lesions were hr-HPV- and p16-negative and in 96% MIB1-expression was confined to the parabasal layers. Eighty-four percent exhibited high p53 labeling indices, sometimes with parabasal extension. Eighty percent of all usual VIN-lesions were hr-HPV-positive, p16-positive, MIB1-positive and p53-negative. Five (of seven) HPV-negative usual VIN lesions, had an expression pattern like the other HPV-positive usual VIN lesions. In conclusion, both pathways leading to vulvar SCC have their own immunohistochemical profile, which can be used to distinguish the 2 types of VIN, but cannot explain differences in malignant potential.

MeSH terms

  • Adult
  • Aged
  • Alphapapillomavirus / genetics
  • Alphapapillomavirus / isolation & purification
  • Biomarkers, Tumor / analysis*
  • Carcinoma in Situ / chemistry
  • Carcinoma in Situ / diagnosis
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • DNA, Viral / isolation & purification
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Papillomavirus Infections / complications
  • Tumor Suppressor Protein p53 / analysis*
  • Tumor Virus Infections / complications
  • Ubiquitin-Protein Ligases / analysis*
  • Vulvar Neoplasms / chemistry*
  • Vulvar Neoplasms / diagnosis*
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Tumor Suppressor Protein p53
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases