Abstract
BackgroundAdenocarcinoma of the periampullary region is associated with poor prognosis and new prognostic and treatment predictive biomarkers are needed for improved treatment. Membranous expression of podocalyxin-like 1(PODXL), which is a cell-adhesion glycoprotein and stem cell marker, has been found to correlate with an aggressive tumour phenotype and adverse outcome in several cancer types. The aim of the present study was to examine the clinicopathological correlates, prognostic and predictive significance of tumour-specific PODXL expression in a retrospective cohort of pancreatic and periampullary carcinoma, morphologically divided into intestinal type (I-type) and pancreatobiliary type (PB-type) tumours.MethodsImmunohistochemical expression of PODXL was analysed in tissue microarrays with primary tumours and a subset of paired lymph node metastases from 175 patients operated with pancreaticoduodenectomy for periampullary adenocarcinoma. Chi square test was applied to analyse the relationship between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox regression models were applied to estimate differences in 5-year overall survival (OS) and recurrence-free survival (RFS) in strata according to membranous and non-membranous PODXL expression.ResultsMembranous PODXL expression was significantly higher in primary PB-type (49.5 %) as compared with I-type (17.5 %) tumours. In PB-type tumours, PODXL expression was significantly associated with female sex (p = 0.005), location to the pancreas (p = 0.005), and poor differentiation grade (p = 0.044). Membranous PODXL expression was significantly associated with a reduced RFS (HR = 2.44, 95 % CI 1.10–5.44) and OS (HR = 2.32, 95 % CI 1.05–5.12) in I-type tumours and with a reduced RFS (HR = 1.63, 95 % CI 1.07–2.49) but not OS in PB-type tumours. PODXL remained a significant independent prognostic factor only in I-type tumours (HR = 5.12, 95 % CI 1.43–18.31 for RFS and HR = 7.31, 95 % CI 2.12–25.16 for OS). Patients with I-type tumours displaying membranous PODXL expression had a significant beneficial effect of adjuvant chemotherapy regarding 5-year OS.ConclusionMembranous expression of PODXL is significantly higher in PB-type than in I-type periampullary adenocarcinomas and an independent factor of poor prognosis in the latter. The results further indicate a beneficial effect of adjuvant chemotherapy on I-type tumours with membranous PODXL expression, suggesting the potential utility of PODXL as a biomarker for improved treatment stratification of these patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12907-015-0009-1) contains supplementary material, which is available to authorized users.
Highlights
Adenocarcinoma of the periampullary region is associated with poor prognosis and new prognostic and treatment predictive biomarkers are needed for improved treatment
Adenocarcinoma of the periampullary region, including tumours originating in the distal bile duct, pancreas, ampulla of Vater and the periampullary duodenum, are a heterogeneous group of neoplasms and despite advances in surgery, radiotherapy, chemotherapy and targeted agents, patients still suffer from a poor prognosis
In intestinal type (I-type) tumours, membranous Podocalyxin-like protein 1 (PODXL) in the metastasis was seen in 1/21 (4.8 %) cases denoted as having non-membranous expression in the primary tumour, and non-membranous PODXL expression in the metastasis was denoted in 2/3 (66.7 %) cases with primary tumours displaying membranous PODXL expression
Summary
Adenocarcinoma of the periampullary region is associated with poor prognosis and new prognostic and treatment predictive biomarkers are needed for improved treatment. Adenocarcinoma of the periampullary region, including tumours originating in the distal bile duct, pancreas, ampulla of Vater and the periampullary duodenum, are a heterogeneous group of neoplasms and despite advances in surgery, radiotherapy, chemotherapy and targeted agents, patients still suffer from a poor prognosis. The incidence of these tumours has markedly increased over the past decades and in 2012 pancreatic cancers of all types were the seventh most common cause of cancer deaths, resulting in 330.000 deaths globally [1]. The present diagnostic and prognostic information provided by histopathological parameters is far from sufficient, strongly implicating the need for additional molecular-based biomarkers to better define clinically relevant subgroups of these tumours for improved treatment stratification
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