This study investigated the immunohistochemical expression of retinoblastoma (RB) protein and p16 protein in 10 neuroendocrine carcinomas (NECs), in comparison to two mixed-type NECs; 28 squamous cell carcinomas (SCCs), and 12 carcinosarcomas (CSs) from patients with esophageal cancer.
The p53 expression was positive in 67.5% of tumor tissue, 20.0% of adjacent non-tumoral tissue and 1.8% of normal esophageal tissue. p16 was positive in 11.6% of esophageal cancer cases and 4.7% of adjacent non-tumoral tissue. p16 was undetectable among control group samples. p53 and p16 levels were not significantly associated with the HPV status.
Epigallocatechin-3-gallate inhibits growth and induces apoptosis in esophageal cancer cells through the demethylation and reactivation of the p16 gene.
Hypermethylation of p16 gene was not found in healthy controls. p53 Pro/Pro genotype was found to be a risk genotype in Northeast India compared with Arg/Pro and Arg/Arg. p53 variant/polymorphism was significantly associated with esophageal cancer risk in the study population under all three genetic models, namely, dominant model (Arg/Pro + Pro/Pro vs Arg/Arg odds ratio = 2.25, confidence interval = 1.19-4.26; p = 0.012), recessive model (Arg/Arg + Arg/Pro vs Pro/Pro odds ratio = 2.35, confidence interval = 1.24-4.44; p = 0.008), and homozygous model (Pro/Pro vs Arg/Arg odds ratio = 3.33, confidence interval = 1.54-7.20; p = 0.002).
Low expression of (or IHC-negative) COX2, miR-200c, ERCC1 and TS, or high expression of (or IHC-positive) CDC25B and p16 are potential biomarkers for predicting the response of esophageal cancer patients treated with chemo(radio)therapy.
Betel quid and tobacco chewing habit synergistically with p16 methylation elevated the risk for esophageal cancer development (adjusted odds ratio (OR) = 6.88, 95% confidence interval (CI) = 1.64-28.81, p = 0.003 for betel quid chewing and adjusted OR = 7.02, 95% CI = 1.87-26.38, p = 0.001 for tobacco chewing).
A tissue microarray containing 86 specimens from esophageal cancer and 40 specimens from adjacent non-cancer tissue was constructed to survey the expression of p53, p16 and COX-2 by immunohistochemistry.
The vast majority of esophageal cancers have inactivation of the p53 and p16 genes at an early stage followed by defects in genes such as APC, Rb and cyclin D1 at later stages of progression.
The relatively low rate of p16 mutation observed here coupled with the high frequency of loss of heterozygosity on chromosome 9 suggests that one or several tumor-suppressor gene(s) distinct from p16 may be the target(s) of allelic deletion in most esophageal cancers or that p16 is inactivated in another way.
These results may have implications regarding the design of clinical trials using p16 gene replacement strategies for intervention in esophageal cancers.
These findings suggest that loss or mutations of the p16 gene are involved in most esophageal cancers and that mutation of this gene plays a critical role in the development of esophageal cancer.