Barrett's Esophagus: Can Biomarkers Predict Progression to Malignancy?
Barrett's esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma. It is characterized histologically by a specialized intestinal metaplasia that replaces the squamous epithelium of the distal esophagus, and is associated with chronic gastroesophageal reflux disease and obesity. Similar to the adenoma-carcinoma sequence of colorectal carcinomas, esophageal adenocarcinoma develops through progression from BE to low- and high-grade dysplasia, then to adenocarcinoma with accumulation of genetic and epigenetic abnormalities. The exact malignancy potential of BE is uncertain. Dysplasia is the most predictive marker for risk of esophageal adenocarcinoma, whereas endoscopic and histological diagnoses are still the gold standard for surveillance of patients with BE. However, both are limited, either by sampling errors in biopsies or by differences in histological interpretation. Several studies have identified candidate biomarkers that may have predictive value and may serve as additional factors for the risk assessment of esophageal adenocarcinoma. This review discusses the role of biomarkers in the progression from BE to adenocarcinoma, focusing on clinical and molecular markers.
Barrett's esophagus (BE) is a premalignant, metaplastic alteration of the distal esophagus that precedes the development of esophageal adenocarcinoma (EA). While the incidence and mortality of distal gastric cancer is decreasing worldwide, EA, which is associated with obesity and gastroesophageal reflux disease (GERD), has the most rapidly rising incidence in the Western world. Interestingly, although 10-20% of the Western population is affected by GERD, BE only occurs in 1-1.5% of the population. Patients with BE have a 30- to 125-fold higher risk of developing EA than those without this lesion. The conversion rate from BE to EA is 0.5-1% per year and less than 5% of patients die of EA, of whom most die from non-neoplastic diseases.
Endoscopic surveillance and histological detection are still the standard methods for the diagnosis of BE. However, both are limited, either by sampling errors or by differences in histological interpretation. Currently, dysplasia (also known as intra-epithelial neoplasia), which is detected histologically, and chromosomal abnormalities (e.g., loss of heterozygosity [LOH] at chromosome 9p and 17p, tetraploidy and aneuploidy) are thought to be the earliest events in the pathogenesis of EA and, therefore, have the most predictive value for risk assessment. However, only histological alterations are of practical value in routine clinical settings.
The uncertainty surrounding the malignancy potential of BE and the lack of possibilities of risk stratification render necessary the identification of new additional predictive markers.
Abstract and Introduction
Abstract
Barrett's esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma. It is characterized histologically by a specialized intestinal metaplasia that replaces the squamous epithelium of the distal esophagus, and is associated with chronic gastroesophageal reflux disease and obesity. Similar to the adenoma-carcinoma sequence of colorectal carcinomas, esophageal adenocarcinoma develops through progression from BE to low- and high-grade dysplasia, then to adenocarcinoma with accumulation of genetic and epigenetic abnormalities. The exact malignancy potential of BE is uncertain. Dysplasia is the most predictive marker for risk of esophageal adenocarcinoma, whereas endoscopic and histological diagnoses are still the gold standard for surveillance of patients with BE. However, both are limited, either by sampling errors in biopsies or by differences in histological interpretation. Several studies have identified candidate biomarkers that may have predictive value and may serve as additional factors for the risk assessment of esophageal adenocarcinoma. This review discusses the role of biomarkers in the progression from BE to adenocarcinoma, focusing on clinical and molecular markers.
Introduction
Barrett's esophagus (BE) is a premalignant, metaplastic alteration of the distal esophagus that precedes the development of esophageal adenocarcinoma (EA). While the incidence and mortality of distal gastric cancer is decreasing worldwide, EA, which is associated with obesity and gastroesophageal reflux disease (GERD), has the most rapidly rising incidence in the Western world. Interestingly, although 10-20% of the Western population is affected by GERD, BE only occurs in 1-1.5% of the population. Patients with BE have a 30- to 125-fold higher risk of developing EA than those without this lesion. The conversion rate from BE to EA is 0.5-1% per year and less than 5% of patients die of EA, of whom most die from non-neoplastic diseases.
Endoscopic surveillance and histological detection are still the standard methods for the diagnosis of BE. However, both are limited, either by sampling errors or by differences in histological interpretation. Currently, dysplasia (also known as intra-epithelial neoplasia), which is detected histologically, and chromosomal abnormalities (e.g., loss of heterozygosity [LOH] at chromosome 9p and 17p, tetraploidy and aneuploidy) are thought to be the earliest events in the pathogenesis of EA and, therefore, have the most predictive value for risk assessment. However, only histological alterations are of practical value in routine clinical settings.
The uncertainty surrounding the malignancy potential of BE and the lack of possibilities of risk stratification render necessary the identification of new additional predictive markers.
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