Abstract
PurposeIntestinal stem cell markers play a significant role in esophageal adenocarcinoma carcinogenesis via Barrett’s esophagus; however, its utility as a prognostic biomarker has not been established.MethodsWe analyzed the immunohistochemical expression of intestinal stem cell markers, ASCL2 and LGR5, using whole slides (35 cases) and tissue microarray (TMA; 64 cases). On TMA slides, adjacent normal squamous epithelium, metaplastic glandular epithelium (Barrett's esophagus), and dysplastic glandular epithelium were inserted when applicable. Two pathologists semi-quantitatively scored stained slides independently, and the results were correlated with clinicopathologic factors and outcomes.ResultsIn whole slides, 51% and 57% expressed high ASCL2 and high LGR5; in TMA, 69% and 88% expressed high ASCL2 and high LGR5, respectively. In TMA, high ASCL2 and low LGR5 expression significantly correlated to a higher number of involved lymph nodes (p=0.027 and p=0.0039), and LGR5 expression significantly correlated to the pathological stage (p=0.0032). Kaplan-Meier analysis showed a negative impact of high ASCL2 expression on overall survival (OS; WS p=0.0168, TMA p=0.0276) as well as progression-free survival (PFS; WS p=0.000638, TMA p=0.0466) but not LGR5. Multivariate Cox regression analysis revealed that ASCL2 expression is an independent prognostic factor for esophageal adenocarcinoma (OS; WS p=0.25, TMA p=0.011. PFS; WS p=0.012, TMA p=0.038). Analysis of the TCGA dataset showed that ASCL2 mRNA levels were correlated to nodal status but not overall survival.ConclusionHigh expression of the intestinal stem cell marker ASCL2 may predict unfavorable outcomes in surgically resected esophageal adenocarcinoma.
Highlights
Esophageal adenocarcinoma (EAC) is one of the least studied cancers and is currently the sixth-leading cause of cancer death globally [1]
In tissue microarray (TMA), high Achaete scute-like 2 (ASCL2) and low Leucinerich-repeat-containing G-protein-coupled receptor 5 (LGR5) expression significantly correlated to a higher number of involved lymph nodes (p=0.027 and p=0.0039), and LGR5 expression significantly correlated to the pathological stage (p=0.0032)
Kaplan-Meier analysis showed a negative impact of high ASCL2 expression on overall survival (OS; whole slides (WS) p=0.0168, TMA p=0.0276) as well as progression-free survival (PFS; WS p=0.000638, TMA p=0.0466) but not LGR5
Summary
Esophageal adenocarcinoma (EAC) is one of the least studied cancers and is currently the sixth-leading cause of cancer death globally [1]. The major pathway to EAC involves gastroesophageal reflux disease resulting in Barrett's esophagus (BE) and subsequent EAC in 0.5%1%. Glandular dysplasia is commonly observed during this process between BE and EAC [1]. BE is characterized by the replacement of normal squamous epithelium of the lower portion of the esophagus with intestinal metaplasia. While BE is the primary precursor lesion and a potent risk factor of EAC, the developmental process from BE to EAC takes about three decades and why some BE progress to EAC but others do not is unknown [3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
