RELATIONSHIP BETWEEN HPV16/18 E6 AND Р53, Р21WAF1, MDM2, KI67 AND CYCLIN D1 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA: COMPARATIVE STUDY BY USING TISSUE MICROARRAY TECHNOLOGY
Z.L. Qi1, X. Huo1, *, X.J. Xu1, B.
Zhang1, M.G. Du2, H.W. Yang1, L.K. Zheng1, J.
Li2, Z.Y. Shen1
1Laboratory Center and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, 515041, P.R. China 2Research center, Shaanxi chaoying Biotechical Company, Xi’an 710061, P.R. China
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, p21Waf1, 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, p21Waf1, 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 < 0.01), p21Waf1 expression — with
these of MDM2 and cyclin D1 (p < 0.01) whilst expression of Ki67 — with ESCC
grade (p < 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.