Prognostic and predictive significance of podocalyxin-like protein expression in pancreatic and periampullary adenocarcinoma

BMC Clinical Pathology

Jakob Eberhard¹  Karin Jirström¹  Björn Nodin¹  Jakob Elebro¹  Margareta Heby¹ 

[1] Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, 221 85, Sweden

关键词: Response prediction;    Prognosis;    Biomarkers;    Immunohistochemistry;    Podocalyxin-like 1;    Pancreatic cancer;    Periampullary adenocarcinoma;   

Others  :  1210953
DOI  :  10.1186/s12907-015-0009-1

 received in 2015-01-29, accepted in 2015-05-18,  发布年份 2015

【 摘 要 】

Background

Adenocarcinoma 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.

Methods

Immunohistochemical 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.

Results

Membranous 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.

Conclusion

Membranous 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.

【 授权许可】

   
2015 Heby et al.; licensee BioMed Central.

【 图 表 】

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