It appears that aneuploidy is linked with specific gene mutations, i.e., of the tumour suppressor gene p53 in chronic ulcerative colitis and in Barrett's esophagus, and of the protooncogene K-ras in colorectal adenomas.
Utilizing immunohistochemistry, p53 staining was detected in 42% of Barrett's metaplasia specimens, most of which were dysplastic, and in 58% of adenocarcinomas.
Esophageal adenocarcinoma is increasing in frequency in the western world at an alarming rate and is unique because there is a clear metaplasia (Barrett's mucosa)/ dysplasia/carcinoma sequence. p53 malfunction arises as an early event in this carcinogenic process and has been demonstrated in patients with nondysplastic Barrett's metaplasia.
We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with BM.
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.
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.
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.
Therefore, to study elevated 4N cell populations in human neoplasia, we used flow cytometry to purify populations of spontaneously arising TP53(wt) and TP53(mut) 4N cells from cell strains derived from premalignant Barrett's esophagus biopsies.
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.
Several investigators have found that p53 alteration is a frequent event in oesophageal adenocarcinomas and is associated with malignant transformation of Barrett's oesophagus. p53 appears to be a promising prognostic marker in Barrett's oesophagus and, as research progresses, possible clinical applications are emerging.
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.
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.
The purpose of this study therefore was to investigate the clinical value of p53 and Ki67 as markers for tumour progression in BE, and at the same time test the validity of the concept of a metaplasia-dysplasia-carcinoma sequence in BE by correlating the expression of these markers with various grades of dysplasia.
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.
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.
Our data strongly suggest that 17p allelic losses precede the development of aneuploidy during neoplastic progression in Barrett's esophagus in vivo and, therefore, support in vitro evidence for the role of p53 in genetic instability.