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Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis.

Fristedt R, Elebro J, Gaber A, Jonsson L, Heby M, Yudina Y, Nodin B, Uhlén M, Eberhard J, Jirström K - PLoS ONE (2014)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.

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.

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Kaplan-Meier estimates of 5-year overall survival according to pIgR expression.Five-year overall survival according to high and low pIgR expression in (A) the entire cohort, (B) intestinal type tumours and (C) pancreatobiliary type tumours.
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pone-0112728-g003: Kaplan-Meier estimates of 5-year overall survival according to pIgR expression.Five-year overall survival according to high and low pIgR expression in (A) the entire cohort, (B) intestinal type tumours and (C) pancreatobiliary type tumours.

Mentions: According to the CRT analysis a prognostic cut-off of 1.892 was adopted (Figure S2). Kaplan-Meier analysis revealed a significantly reduced 5-year OS for patients with tumours displaying low pIgR expression (logrank p<0.001, Figure 3A). In subgroup analysis by morphological type, this association remained significant for intestinal type (duodenum and ampullary intestinal type) tumours (logrank p = 0.003, Figure 3B), but not in pancreatobiliary type (ampulla-pancreatobiliary type, distal bile duct and pancreatic) tumours (logrank p =  0.136, Figure 3C). Similar trends were seen for RFS (Figure 4 A–C).


Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis.

Fristedt R, Elebro J, Gaber A, Jonsson L, Heby M, Yudina Y, Nodin B, Uhlén M, Eberhard J, Jirström K - PLoS ONE (2014)

Kaplan-Meier estimates of 5-year overall survival according to pIgR expression.Five-year overall survival according to high and low pIgR expression in (A) the entire cohort, (B) intestinal type tumours and (C) pancreatobiliary type tumours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232506&req=5

pone-0112728-g003: Kaplan-Meier estimates of 5-year overall survival according to pIgR expression.Five-year overall survival according to high and low pIgR expression in (A) the entire cohort, (B) intestinal type tumours and (C) pancreatobiliary type tumours.
Mentions: According to the CRT analysis a prognostic cut-off of 1.892 was adopted (Figure S2). Kaplan-Meier analysis revealed a significantly reduced 5-year OS for patients with tumours displaying low pIgR expression (logrank p<0.001, Figure 3A). In subgroup analysis by morphological type, this association remained significant for intestinal type (duodenum and ampullary intestinal type) tumours (logrank p = 0.003, Figure 3B), but not in pancreatobiliary type (ampulla-pancreatobiliary type, distal bile duct and pancreatic) tumours (logrank p =  0.136, Figure 3C). Similar trends were seen for RFS (Figure 4 A–C).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden.

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.

Show MeSH
Related in: MedlinePlus