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.
Highlights
Adenocarcinomas arising in the pancreas and periampullary region are a heterogeneous group of neoplasms with the common feature of being highly aggressive and challenging to treat
Results polymeric immunoglobulin receptor (pIgR) expression in primary tumours and paired metastases pIgR expression could be evaluated in all 50 samples with nonmalignant tissue, in 172/175 (98.3%) of the primary tumours and in 96/105 (89.5%) of the sampled lymph node metastases
A total number of 25 (14.5%) primary tumours and 20 (20.8%) metastases were completely negative for pIgR expression, and in the other cases, pIgR was expressed in varying fractions and intensities
Summary
Adenocarcinomas arising in the pancreas and periampullary region are a heterogeneous group of neoplasms with the common feature of being highly aggressive and challenging to treat. 15–20% of the tumours are resectable at presentation [1], and there is an obvious lack of effective neoadjuvant-, adjuvant- and palliative radio-chemotherapeutic options, even with the advent of gemcitabine. Pancreatic cancer is the fourth most common cause of cancer related death, and the death rate has stayed stable over many years. Morphological type seems to provide more important prognostic information than the tumour origin, with pancreatobiliary versus intestinal differentiation being associated with significantly shorter survival rates [5,6]. Given the dismal prognosis for the group of pancreatic and periampullary carcinomas as a whole, the diagnostic and prognostic information provided by histopathological parameters is far from sufficient. There is a great need for additional molecular-based biomarkers, to better define clinically relevant subgroups of these tumours, and, pave the way for novel treatment strategies
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