Abstract
BackgroundPodocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma.MethodsThe study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor.ResultsIn the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039).ConclusionsIn esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12907-016-0034-8) contains supplementary material, which is available to authorized users.
Highlights
Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies
Expression of podocalyxin-like protein (PODXL) was significantly higher in intestinal metaplasia (Barrett’s esophagus or gastric intestinal metaplasia) compared to normal epithelium (p < 0.001) and PODXL expression was significantly higher in primary tumors and lymph node metastases compared to intestinal metaplasia (p < 0.001)
There was no significant difference in PODXL expression between primary tumors and lymph node metastases (p = 0.645) and PODXL expression in primary tumors and/or lymph node metastases did not differ significantly by primary tumor location (p = 0.314, data not shown)
Summary
Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma. The majority of esophageal cancers were squamous cell carcinomas, but in the last four decades there has been a drastic increase in the incidence of adenocarcinoma, especially in many Western countries, where it is the most common subtype [2]. Proposed risk factors for esophageal and EG junction adenocarcinoma are gastroesophageal reflux disease, obesity and decreased prevalence of Helicobacter pylori infection [4, 5]. The incidence has been declining for several decades [6], possibly due to improved sanitary conditions and decreased prevalence of Helicobacter pylori infection [7], but globally it is still the 3rd leading cause of cancer death. The prognosis is still poor, especially in Western populations, with 5-year survival rates less than 40 %
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