Relationship between HPV16/18 E6 and 53, 21WAF1, MDM2, Ki67 and cyclin D1 expression in esophageal squamous cell carcinoma: comparative study by using tissue microarray technology

Exp Oncol. 2006 Sep;28(3):235-40.

Abstract

Aim: To investigate the role of human papillomavirus (HPV) HPV16/18 E6 oncogene in the carcinogenesis of esophageal cell carcinoma (ESCC).

Materials and methods: Tissue microarray (TMA) block was constructed from 60 cases of paraffin-embedded ESCC tissues and pair-matched controls (adjacent normal epithelium). Immunohistochemistry (IHC) methods were applied to detect the expression of HPV16/18 E6, p53, p21(WAF1), MDM2, Ki67 and cyclin D1 proteins on TMA slides. In situ hybridization (ISH) targeting HPV gene was also used.

Results: In ESCC samples, 18.3% (11/60) were revealed HPV16/18 E6 positive by IHC, while 40.0% (24/60) HPV positive by ISH; HPV16/18 E6 expression was significantly higher than that of control samples. In ESCC samples, the expressions of p53, p21(WAF1), Cyclin D1, MDM2 and Ki67 were recorded in 60.0% (36/60), 40.0% (24/60), 51.7% (31/60), 65.0% (39/60) and 88.3% (53/60) cases respectively, In ESCC samples, p53, MDM2 and Ki67 expression correlated with the HPV16/18 E6 expression (p less, similar 0.01), p21(WAF1) expression - with these of MDM2 and cyclin D1 (p less, similar 0.01) whilst expression of Ki67 - with ESCC grade (p less, similar 0.01).

Conclusion: HPV might be one of etiological factor of esophageal carcinoma in Shantou, China. p53, MDM2 proteins may play important roles in the pathogenesis of HPV-associated ESCC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology*
  • Cyclin D
  • Cyclin-Dependent Kinase Inhibitor p21 / analysis
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclins / analysis
  • Cyclins / metabolism
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Esophageal Neoplasms / chemistry
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / virology*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral / analysis
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / analysis
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Repressor Proteins / analysis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin D
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Ki-67 Antigen
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2