title: Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: David
authors.identifier: 0000-0001-9461-7391
authors.initials: D
authors.lastname: Borg
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Hedner
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Johnsson
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
keywords: Adenocarcinoma; Esophageal neoplasms; PODXL; Prognosis; Stomach neoplasms