Biomarkers in Barrett's esophagus and esophageal adenocarcinoma: predictors of progression and prognosis.

MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Box 197/ Hills Road, Cambridge, CB20XZ, United Kingdom.
World Journal of Gastroenterology (Impact Factor: 2.37). 12/2010; 16(45):5669-81.
Source: PubMed


Barrett's esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett's esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett's esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett's esophagus and EA and to discuss what is required to move the field forward towards clinical application.

  • Source
    • "Of the 3059 articles returned, 2364 were excluded on review of title and 482 on examination of abstract, leaving 214 articles considered relevant. Crosschecking of existing systematic review reference lists revealed no further relevant articles (Vallbohmer and Lenz, 2006; Ong et al, 2010; Chan et al, 2012; Chen et al, 2012, 2013; Peng et al, 2013; Gowryshankar et al, 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers. Relevant articles were identified via Ovid medline 1946-2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis. A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15-3.79), CD3 (HR=0.51, 95% CI=0.32-0.70), CD8 (HR=0.55, CI=0.31-0.80) and EGFR (HR=1.65, 95% CI=1.14-2.16). Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.British Journal of Cancer advance online publication, 25 June 2015; doi:10.1038/bjc.2015.179
    Full-text · Article · Jun 2015 · British Journal of Cancer
  • Source
    • "In EAC, targeted copy number aberration (CNA) studies have shown significant associations with survival (Brien et al., 2000; Pasello et al., 2009; Schoppmann et al., 2010; Thompson et al., 2011), as have immunohistochemistry-based studies of proteins whose genes are known to be frequent sites of CNA [e.g., ERBB2 (Polkowski et al., 1999; Langer et al., 2006)]. Validation of findings from these targeted studies in independent cohorts has proved difficult, no doubt in part due to methodological differences (Ong et al., 2010). A number of moderate to high density genome-wide CNA studies have also been performed (Walch et al., 2000; Riegman et al., 2001; Varis et al., 2001; Weiss et al., 2003; Albrecht et al., 2004; Nancarrow et al., 2008; Pasello et al., 2009; Paulson et al., 2009; Wiech et al., 2009; Gu et al., 2010; Goh et al., 2011; Bandla et al., 2012), although few of these address prognosis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of esophageal adenocarcinoma (EAC) has been increasing rapidly for the past 3 decades in Western (Caucasian) populations. Curative treatment is based around esophagectomy, which has a major impact on quality of life. For those suitable for treatment with curative intent, 5-year survival is ∼30%. More accurate prognostic tools are therefore needed, and copy number aberrations (CNAs) may offer the ability to act as prospective biomarkers in this regard. We performed a genome-wide examination of CNAs in 54 samples of EAC using single-nucleotide polymorphism (SNP) arrays. Our aims were to describe frequent regions of CNA, to define driver CNAs, and to identify CNAs that correlated with survival. Regions of frequent amplification included oncogenes such as EGFR, MYC, KLF12, and ERBB2, while frequently deleted regions included tumor suppressor genes such as CDKN2A/B, PTPRD, FHIT, and SMAD4. The genomic identification of significant targets in cancer (GISTIC) algorithm identified 24 regions of gain and 28 regions of loss that were likely to contain driver changes. We discovered 61 genes in five regions that, when stratified by CNA type (gain or loss), correlated with a statistically significant difference in survival. Pathway analysis of the genes residing in both the GISTIC and prognostic regions showed they were significantly enriched for cancer-related networks. Finally, we discovered that copy-neutral loss of heterozygosity is a frequent mechanism of CNA in genes currently targetable by chemotherapy, potentially leading to under-reporting of cases suitable for such treatment. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Apr 2014 · Genes Chromosomes and Cancer
  • Source
    • "It is present in 77% of noncardia gastric cancers [10] and in 90% of all chronic gastritis patients, so has been associated with increased risk of cancer up to nine times [11] [12]. Although different genetic and epigenetic alteration involving oncogenes activation, tumor suppressor genes mutations, DNA repair genes, microsatellite instability, loss of heterozygosity (LOH) have been reported in both esophageal and gastric cancers [2] [3] [13] [14], genetic alterations in TP53 tumor suppressor gene are fundamental events related in both early stage and advanced tumor. "
    [Show abstract] [Hide abstract]
    ABSTRACT: TP53 genes is one of more important tumor suppressor gene, which acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. The development of esophageal and gastric cancers is a multistep process resulting in successive accumulation of genetic alterations that culminates in the malignant transformation. Thus, this study highlights the participation of the main genetic alterations of the TP53 gene in esophageal and gastric carcinogenesis. Among these changes, high frequency of TP53 mutations, loss of heterozygosity (LOH), overexpression of the p53 protein, and consequently loss of p53 function, which would be early events in esophageal and gastric cancers, as well as an important biomarker of the prognosis and treatment response. Furthermore, Single Nucleotide Polymorphisms (SNPs) of TP53 have been implicated in the development and prognosis of several cancers, mainly TP53 codon 72 polymorphism whose role has been extensively studied in relation to susceptibility for esophageal and gastric cancer development.
    Full-text · Article · Aug 2012 · BioMed Research International
Show more