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Gene Implications in esophageal adenocarcinoma Ref.
TLR4 Toll-like receptor 4 (TLR4) is mutated in 6% of esophageal adenocarcinoma[ 3 ]
TP53 Tumor protein p53 (TP53) substitution or truncation in approximately 83%
of patients with esophageal adenocarcinoma[ 5 ]TP53-mutant cells go through genome doubling, which proceeds to
attainment of oncogenic amplification[ 10 ]Mutation of TP53 was indicative of high-grade dysplasia in BE or
esophageal adenocarcinoma occurrences, occurring during the transition
from low-grade to high-grade dysplasia[ 2 , 9 ]Patients without TP53 mutation did not develop high-grade dysplasia or
metaplasia[ 11 ]Homozygote mutant in MFD-1 cell line on chromosome 17 at position
7577120[ 32 ]TP53 mutation was not found in human papillomavirus (HPV)-positive
esophageal adenocarcinoma but was found in some HPV-negative
esophageal adenocarcinoma cases[ 19 , 20 ]47% patients with esophageal adenocarcinoma had TP53 mutation and had
reduced 5-year overall survival[ 17 ]TP53 mutations and deletion do not occur commonly; however,
accumulation of the protein is common, suggesting an alternative
mechanism responsible for the common TP53 immunochemistry
detection[ 12 ]DNA sequencing detected more TP53 mutation than immunohistochemical
staining (75% by sequencing vs 58% by immunohistochemistry). TP53
mutation was not detected in the remaining 25% of esophageal
adenocarcinoma indicating that it is insufficient to function by itself as a
single biomarker for Barrett esophagus monitoring but could play a role
in a panel of biomarkers due to its high specificity[ 13 ]33–73% of patients with esophageal adenocarcinoma had TP53 mutation
while 0–4% of patients with Barrett esophagus had no TP53 mutation
suggesting that TP53 mutation presents much later in the progression
from Barrett esophagus to esophageal adenocarcinoma and is not a good
prognostic marker for risk of progression from Barrett esophagus to
esophageal adenocarcinoma[ 11 , 14 , 18 ,
36 , 38 ]In most cases, TP53 mutation was associated with poor tumor
differentiation, advanced tumor/nodes/metastasis (TNM) stages, and
lymph node metastasis except for one study, which claimed that the
mutation was in well-differentiated adenocarcinomas[ 11 , 17 ,
18 ]VSIG10L V-Set And Immunoglobulin Domain Containing 10 Like (VSIG10L) is a
candidate for a familial Barrett esophagus and subsequently esophageal
adenocarcinoma susceptibility gene
[ 6 ]Table 1
(continued)
Katherine T. W. Lee et al.