Heby Margareta, Elebro Jakob, Nodin Björn, Jirström Karin, Eberhard Jakob
Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85 Lund, Sweden.
BMC Clin Pathol. 2015 May 30;15:10. doi: 10.1186/s12907-015-0009-1. eCollection 2015.
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.
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.
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.
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.
壶腹周围腺癌预后较差，需要新的预后和治疗预测生物标志物以改善治疗效果。多配体蛋白聚糖样蛋白1（PODXL）是一种细胞粘附糖蛋白和干细胞标志物，其膜表达已被发现与几种癌症类型的侵袭性肿瘤表型和不良预后相关。本研究的目的是在一组回顾性的胰腺和壶腹周围癌队列中，研究肿瘤特异性PODXL表达的临床病理相关性、预后及预测意义，这些肿瘤在形态学上分为肠型（I型）和胰胆管型（PB型）肿瘤。
对175例行胰十二指肠切除术治疗壶腹周围腺癌患者的组织芯片进行分析，检测原发性肿瘤及配对淋巴结转移灶中PODXL的免疫组化表达。采用卡方检验分析PODXL表达与临床病理参数之间的关系。应用Kaplan-Meier分析和Cox回归模型，根据PODXL的膜表达和非膜表达，估计各亚组5年总生存率（OS）和无复发生存率（RFS）的差异。
原发性PB型肿瘤（49.5%）的膜PODXL表达显著高于I型肿瘤（17.5%）。在PB型肿瘤中，PODXL表达与女性性别（p = 0.005）、胰腺部位（p = 0.005）及低分化程度（p = 0.044）显著相关。膜PODXL表达与I型肿瘤的RFS降低（HR = 2.44，95%CI 1.10 - 5.44）和OS降低（HR = 2.32，95%CI 1.05 - 5.12）显著相关，与PB型肿瘤的RFS降低（HR = 1.63，95%CI 1.07 - 2.49）相关，但与OS无关。PODXL仅在I型肿瘤中仍是一个显著的独立预后因素（RFS的HR = 5.12，95%CI 1.43 - 18.31；OS的HR = 7.31，95%CI 2.12 - 25.16）。I型肿瘤中显示膜PODXL表达的患者在5年OS方面从辅助化疗中获得显著益处。
PB型壶腹周围腺癌的膜PODXL表达显著高于I型，且是I型预后不良的独立因素。结果进一步表明辅助化疗对膜PODXL表达的I型肿瘤有有益作用，提示PODXL作为生物标志物对改善这些患者的治疗分层可能具有实用性。
