The ORs of p16 methylation for genotype CT and TT were 1.98 (95% CI 1.01-3.89) and 17.79 (95% CI 2.26-140.22) in EPL, 4.86 (95% CI 2.48-9.50) and 20.40 (95% CI 2.53-164.81) in ESCC, respectively.
Consistent with the immunohistochemistry results, p16 was expressed in tumor tissue from nude mice that had been transplanted with the modified human ESCC lines.
<b>CONCLUSIONS:</b> These results suggest that hr-HPV types are not associated with the development of ESCC and that p53 and p16 protein expression have no relationship with HPV infection in normal or cancerous esophagus.
By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival.
PubMed, EMBASE, and the Cochrane Library were systematically searched with the purpose of identifying all studies published between January 1980 and July 2013 reporting both HPV and p16 results in a minimum of five human ESCC specimens.
Abnormal expression of p16 and p53, but not MDM2, was significantly higher in the tumoral tissue. p53 was concomitantly accumulated in ESCC tumor along with MDM2 overexpression and p16 negative expression.
In the present investigation, we have studied the role of p16 promoter methylation in 69 histopathologically confirmed ESCC tissues and compared it with corresponding normal adjacent tissues for DNA methylation in the CpG island in the p16 promoter region by methylation-specific polymerase chain reaction (MSP) and p16 protein expression by immunoblotting.
This indicates that p16 promoter methylation suppresses p16 expression and that the loss of expression has a close relationship with poor prognosis in patients with ESCC.
In total 95 lesion tissues of EPC and ESCC, p16 methylation was found in 53 (55.79%) cases, and 41 of 53 (77.36%) cases were demonstrated deletion of the p16 protein immunohistochemically.
Matrigel invasion assays of p16-deleted ESCC cells showed that restoring wild-type p16 activity into the cells significantly inhibits tumor-cell invasion, suggesting that p16 inactivation could be involved in ESCC invasion.
Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.
The immunohistochemical studies of ESCC primary tumor specimens showed that loss of p16 expression was significantly correlated with VEGF-positive expression (p = 0.0004).
High frequency of simultaneous loss of p16 and p16beta gene expression in squamous cell carcinoma of the esophagus but not in adenocarcinoma of the esophagus or stomach.