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


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).


CONCLUSIONS
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.
Qi
Z L
ZL
Laboratory Center and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, 515041, PR China. xhuo@stu.edu.cn
Huo
X
X
Xu
X J
XJ
Zhang
B
B
Du
M G
MG
Yang
H W
HW
Zheng
L K
LK
Li
J
J
Shen
Z Y
ZY
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000378:metabolism; D016213:Cyclins / Q000032:analysis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism
C493956:CDKN1A protein, human; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D019394:Ki-67 Antigen; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2