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

Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort.

Risk factors for breast cancer vary according to breast cancer subtype. This study analyzes the impact of potential risk factors in breast cancer by androgen receptor (AR) status

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis. There is a need to identify prognostic subtypes of PDAC to predict clinical and therapeutic outcomes accurately, and define novel therapeutic targets. The purpose of this review was to provide a systematic summary and review of available data on immunohistochemical (IHC) prognostic and predictive markers in patients with PDAC. METHODS: Relevant articles in English published between January 1990 and June 2010 were obtained from PubMed searches. Other articles identified from cross-checking references and additional sources were reviewed. The inclusion was limited to studies evaluating IHC markers in a multivariable setting. RESULTS: Database searches identified 76 independent prognostic and predictive molecular markers implicated in pancreatic tumour growth, apoptosis, angiogenesis, invasion and resistance to chemotherapy. Of these, 11 markers (Ki-67, p27, p53, transforming growth factor β1, Bcl-2, survivin, vascular endothelial growth factor, cyclo-oxygenase 2, CD34, S100A4 and human equilibrative nucleoside transporter 1) provided independent prognostic or predictive information in two or more separate studies. CONCLUSION: None of the molecular markers described can be recommended for routine clinical use as they were identified in small cohorts and there were inconsistencies between studies. Their prognostic and predictive values need to be validated further in prospective multicentre studies in larger patient populations. A panel of molecular markers may become useful in predicting individual patient outcome and directing novel types of intervention