Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma

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.

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

“…A study employing tissue microarrays and 2 antibodies (HPA2110 and HES9) to evaluate PODXL expression in GC tumors from 337 patients demonstrated the prognostic role of PODXL in GC . Similarly, a study of 174 patients with esophageal or gastric adenocarcinoma revealed that PODXL expression was an independent prognostic biomarker for reduced time to recurrence and poor OS . Here, we used the IHC method to detect PODXL expression in GC tissues and their corresponding NAT.…”

“…This was the only evidence that PODXL served as a biomarker in breast cancer with good prognosis . To the best of our knowledge, there are few reports on the mechanism of PODXL in GC progression, although there are reports of the poor prognostic value of PODXL expression for GC patients . RUN and FYVE domain containing 1 (RUFY1) is a member of the RUFY family, whose members contain an N‐terminal RUN domain and a C‐terminal FYVE domain .…”

Identification of LEA, a podocalyxin‐like glycoprotein, as a predictor for the progression of colorectal cancer

“…It was first discovered in renal podocytes as an antiadhesive protein with the molecular weight of 160‐165 kDa and later found to be expressed in vascular endothelium and involved in hematopoiesis and neural development . Recently, aberrant PODXL expression was observed in several different types of cancers including breast cancer, bladder cancer, renal cancer, prostate cancer, pancreatic adenocarcinoma, and gastric adenocarcinoma . Sizemore et al found that PODXL increased the aggressive phenotype of breast cancer and prostate cancer.…”

“…Sizemore et al found that PODXL increased the aggressive phenotype of breast cancer and prostate cancer. In both pancreatic and periampullary adenocarcinoma and esophageal and gastric adenocarcinoma, PODXL was proven to be an independent predictor of poor outcome . In the case of CRC, Larsson et al detected PODXL using antibody HPA2110 and analyzed its expression levels in 536 CRC cases, demonstrating that the PODXL was an independent factor of poor prognosis and may be a useful marker to stratify patients for adjuvant chemotherapy.…”

“…[23][24][25][26] Recently, aberrant PODXL expression was observed in several different types of cancers including breast cancer, bladder cancer, renal cancer, prostate cancer, pancreatic adenocarcinoma, and gastric adenocarcinoma. [27][28][29][30][31][32] Sizemore et al 30 found that PODXL increased the aggressive phenotype of breast cancer and prostate cancer. In both pancreatic and periampullary adenocarcinoma and esophageal and gastric adenocarcinoma, PODXL was proven to be an independent predictor of poor outcome.…”