Aims: Gastroesophageal adenocarcinomas are common and highly lethal malignancies. There is growing evidence to support the central role of cancer stem cells (CSCs) in the development and progression of metastasis. Numerous studies have shown poor clinical outcomes associated with expression of the CSC markers CD44, CD133 and ALDH1 in locoregional gastroesophageal cancer. We aimed to investigate the prognostic significance associated with expression of CSC markers in metastatic gastroesophageal cancer for which data is lacking.
Methods: Immunohistochemical staining for CD44, CD133, ALDH1 and the metastatic biomarker urokinase plasminogen activator receptor (uPAR) was performed using metastatic gastroesophageal adenocarcinomas deposits and scored by two independent pathologists. Retrospective patient data including demographic information, clinicopathological features and mortality were obtained from clinical records. Univariate and multivariate analysis was performed using SAS 9.2 software to determine the association of CSC expression with clinicopathological factors, uPAR expression, and overall survival (OS).
Results: Of the 36 patients included in the study, 16 (44%) were positive for CD44, 13 (36%) were positive for CD133, and 26 (72%) were positive for ALDH1. CD44 expression was significantly associated with poorer OS in univariate (HR 2.9 95%CI 1.3 – 6.9, p=0.008) and multivariate analyses (HR 2.5 95%CI 1.1 – 6.2, p=0.04). ALDH1 expression was significantly associated with poorer OS in univariate (HR 2.4 95% CI 1.01 – 5.7, p=0.04) analysis but was not significant in multivariate analysis. Both CD44 and ALDH1 expression were significantly associated with uPAR expression. We found no association between CD133 expression and OS.
Conclusions: CD44 expression on metastatic disease from gastroesophageal adenocarcinomas is an independent prognostic marker associated with poorer OS. We also show co-expression of CSC markers and uPAR in gastroesophageal cancers, which provides further evidence of the invasive properties of CSCs. These results expand current evidence to support the role of CSCs as biomarkers in metastatic gastroesophageal cancer.