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

Qi Z.L., Huo X., Xu X.J., Zhang B., Du M.G., Yang H.W., Zheng L.K., Li J., Shen Z.Y.

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.

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