Aneuploidy on a Brush - A New Approach to Detecting Cancer and Pre-Cancers of the Esophagus

Esophageal adenocarcinoma [EAC] is the fastest growing in incidence cancer in the US over the last 25 years, while also having a 5 year survival of less than 20%. Barrett’s Esophagus [BE] which occurs in up to 5% of the population, is the only known precursor of EAC and caused by gastric reflux. Once identified, patients with BE undergo lifelong endoscopic surveillance with multiple biopsies taken for pathology review– even though their individual lifetime risk of EAC is small. This is an extremely costly and inconvenient process which, among other issues, is also associated with pathology ‘overcalling’ of precancerous changes leading to significant overtreatments.

Aneuploidy has long been proposed as a tool of EAC progression risk assessment in BE patients but due to a number of issues has not been implemented as a clinical test. We recently assessed whether an esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to interrogate ~350,000 genome-spanning regions and identify chromosome arm alterations to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer.

Our results demonstrate the feasibility of combining aneuploidy with chromosomal changes of a limited gene panel to accurately define BE patients with BE-associated cancer and pre-cancerous changes. The clinical implications of this approach are now being proposed for prospective trials. 

Learning Objectives:

1. Discuss the increasing healthcare burden of esophageal cancer.

2. Discuss the morphologic and molecular basis for esophageal cancer.

3. Identify the opportunities for use of molecular changes to identify patients at high risk of esophageal cancer.