Reduced Expression of the Polymeric Immunoglobulin Receptor in Pancreatic and Periampullary Adenocarcinoma Signifies Tumour Progression and Poor Prognosis

Abstract

The polymeric immunoglobulin receptor (pIgR) is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001–2011. Tissue microarrays were constructed from primary tumours (n = 175) and paired lymph node metastases (n = 105). A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR) for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3%) primary tumours and in 96/105 (91.4%) lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p = 0.018). Low pIgR expression was significantly associated with poor differentiation grade (p<0.001), perineural growth (p = 0.027), lymphatic invasion (p = 0.016), vascular invasion (p = 0.033) and infiltration of the peripancreatic fat (p = 0.039). In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR = 2.99, 95% confidence interval (CI) 1.71–5.25) and early recurrence (HR = 2.89, 95% CI 1.67–4.98). This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10–3.57). These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies a more favourable tumour phenotype and that low expression independently predicts a shorter survival in patients with pancreatic and periampullary cancer. The mechanistic basis for the putative tumour suppressing properties of pIgR in these cancers merits further study.

Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags

“…It binds polymeric immunoglobulin molecules and presents them at the mucosal lining of the gastrointestinal tract and exocrine glands ( Phalipon and Corthesy, 2003 ). The finding that high PIGR expression is associated with more favourable clinic-pathological characteristics and its loss with an adverse clinical outcome is in line with the vast majority of published studies in a number of cancers, for example, pancreatic, gastro-oesophageal, ovarian, bladder, colon and non-small cell lung cancer ( Fristedt et al , 2014 ). In this study, the serum PIGR levels in PDAC patients were significantly greater than in HVs.…”

Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome

“…The downregulation of CROCC was associated with poor survival in patients with hepatocellular carcinoma after surgical resection 38 . PIGR, that encodes for polymeric immunoglobulin receptor 26 , was found to be downregulated in pancreatic 39 and periampullary adenocarcinoma 39 and lung cancer 40 . The upregulation of IGFBP4 (encodes for a protein that binds insulin-like growth factors I and II 26 ), was shown to function as a potent tumor suppressor in hepatocellular carcinoma and delay tumor formation in prostate cancer cells 41 , 42 .…”

Prognostic impact of tumour-associated B cells and plasma cells in epithelial ovarian cancer

“…Furthermore, CD20 expression was revealed to have an inverse relationship with tumour-specific expression of PIGR, a receptor that binds polymeric immunoglobulin molecules at the surface of epithelial cells. High expression of PIGR has been demonstrated to correlate with an improved patient outcome in several cancer forms including EOC [ 16 , 43 – 46 ] and, speculatively, this may be attributed to a negative regulatory function of PIGR on B-cell TILs, or vice versa.…”