Somatic mutations in key genes including TP53 occur early in the neoplastic progression sequence of Barrett's esophagus, whereas chromosomal amplification resulting in oncogene activation occurs as a critical late event.
In this case-control sample set, TP53 mutations in BE tissues increased the adjusted risk of progression 13.8-fold (95% confidence interval, 3.2-61.0) (P < .001).
We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with BM.
Aberrant p53 expression in BE patients appeared to be associated with a significantly increased risk of neoplastic progression for both non-dysplastic and LGD BE patients.
This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6/E7, respectively.
Although p53 is a promising marker for identifying high-risk BE patients, it is not recommended for routine use at present; additional studies are needed to address questions regarding case selection, interpretation, integration with morphologic diagnosis, and impact on clinical outcome.
Results showed that: (i) early BE molecular alterations are mainly localized proximal to, or within, TP53 gene; (ii) LOH events present in cfDNA not only retrace the time-matched biopsy profile but better represent the total alterations of the BE epithelium.
In order to provide an unbiased extraction of the knowledge from the literature, a text-mining methodology was used to select genes that are involved in the BE progression, with the top candidate genes found to be TP53, CDKN2A, CTNNB1, CDH1, GPX3, and NOX5.
Next-generation sequencing panels for detection of TP53 and possibly combined mutations in other genes, such as APC and CDKN2A, may be useful in the clinical setting to improve dysplasia and cancer surveillance in patients with Barrett's esophagus.
Our analysis showed that oncogene amplification typically occurred as a late event and that TP53 mutations often occurred early in Barrett's esophagus progression, including in non-dysplastic epithelium.
Frequent somatic mutations in the tumor suppressor genes CDKN2A and TP53 were recently reported in EA tumors, while somatic alterations at 9p (CDKN2A) and 17p (TP53) have been implicated as predictors of progression from BE to EA.
Cdx2, mucin (MUC) series (MUC2, MUC5AC and MUC6), p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.
Accumulation of p53 was seen several years before development of HGD/EAC, and may therefore be an early marker in BE at a stage when dysplasia is not yet detected.
Esophageal biopsies from 243 patients with BE were evaluated at baseline for TP53 and CDKN2A (p16) alterations, tetraploidy, and aneuploidy using sequencing; loss of heterozygosity (LOH); methylation-specific PCR; and flow cytometry.
We concluded that p53 is insufficient as a single marker for Barrett's esophagus monitoring but may be useful as part of a panel due to its high specificity.