Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis.
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.
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Richard
R
Fristedt
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Jacob
J
Elebro
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Alexander
A
Gaber
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Liv
L
Jonsson
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Margareta
M
Heby
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Yulyana
Y
Yudina
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Björn
B
Nodin
Science for Life Laboratory, Royal Institute of Technology, 171 21 Stockholm, Sweden; School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, 106 91 Stockholm, Sweden.
Mathias
M
Uhlén
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Jakob
J
Eberhard
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.
Karin
K
Jirström
D014670:Ampulla of Vater / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D046888:Tissue Array Analysis
D019056:Receptors, Polymeric Immunoglobulin