In Sweden, EOC accounts for 3

In Sweden, EOC accounts for 3.1% of all cancers and 5.9% of all cancer deaths in women [2]. tubes (n = 38) and omental metastases (n = 33) were also analysed. Kaplan-Meier analysis and Cox regression analysis were applied to examine the impact of PIGR expression on overall survival (OS) and ovarian cancer-specific survival (OCSS). == Results == PIGR expression was significantly higher in fallopian tubes compared to primary tumours and metastases (p < 0.001) and lower in carcinoma of the serous subtype compared to other carcinomas (p < 0.001). PIGR expression was significantly associated with lower grade (p = 0.001), mucinous histological subtype (p = 0.002), positive progesterone receptor expression (p = 0.009) and negative or low Ki-67 expression (p = 0.003). Kaplan-Meier analysis revealed a significantly improved OS (p = 0.013) and OCSS (p = 0.009) for patients with tumours displaying high expression of PIGR. These associations were confirmed in unadjusted Cox regression analysis (HR = 0.48; 95% CI 0.26-0.87; p = 0.015 for OS and HR = 0.43, 95% CI 0.22-0.82; p = 0.011 for OCSS) but did not remain significant after adjustment for age, grade and clinical stage. == Conclusions == This study provides a first demonstration of PIGR expression in human fallopian tubes, primary EOC tumours and metastases. High tumour-specific expression of PIGR was found to be associated with a favourable prognosis in unadjusted, but not in adjusted, analysis. These findings are novel and merit further investigation. Keywords:Polymeric immunoglobulin receptor, Fallopian tubes, Ovarian cancer, Prognosis == Introduction == Epithelial ovarian cancer (EOC) is the fifth RH-II/GuB most common cancer type in women BMS 599626 (AC480) in more developed areas and the most lethal malignancy of the female reproductive tract [1]. In Sweden, EOC accounts for 3.1% of all cancers and 5.9% of all cancer deaths in women [2]. Due to vague symptomatology and the absence of reliable screening assessments [3], the majority of EOC patients are diagnosed in advanced BMS 599626 (AC480) clinical stages, having stage III and IV tumours, with poor 5-year survival rates [4]. Hence, there is a need to identify novel diagnostic, prognostic and treatment predictive biomarkers. Using the Human Protein Atlas (http://www.proteinatlas.org) as a tool for antibody based biomarker discovery [5], the polymeric immunoglobulin receptor (PIGR) was recently identified as being differentially expressed among EOC samples, with either negative or strong cytoplasmic and membranous staining. Thus, we hypothesized that PIGR might be a putative prognostic biomarker in EOC. PIGR is a member of the immunoglobulin superfamily that binds polymeric immunoglobulin molecules at the basolateral surface of epithelial cells. The complex is then transcytosed across the cell to be modified and secreted at the apical surface as secretory component (SC) [6]. SC ensures effective mucosal secretion of polymeric immunoglobulins [6]. The clinicopathological significance of PIGR has hitherto only been investigated in a few studies. PIGR-negative adenocarcinomas in the distal oesophagus and gastroesophageal junction have been found to be more aggressive and to possess higher metastatic potential compared to adenocarcinomas with high expression of PIGR [7]. Low expression of PIGR in colorectal cancer was found to be associated with tumourigenicity [8] and with poor prognosis [9]. Furthermore, tumour progression in non-small cell lung cancer is usually reportedly associated with loss of PIGR expression [10]. One study reported associations between high expression of PIGR and type 1 endometrial cancer, suggesting a possible explanation for this BMS 599626 (AC480) less aggressive type [11]. On the contrary, overexpression of PIGR in hepatitis B-derived hepatocellular carcinoma has been described to correlate with higher metastatic potential and poor prognosis [12]. A study concerning bladder cancer lays forward a hypothesis that PIGR expression is associated with good prognosis, however, the study also points out the need for further research [13]. PIGR expression has not yet been described in EOC and consequently, this study will be novel. The aim of this study was to evaluate the clinicopathological correlates and prognostic value, of PIGR expression in EOC, by immunohistochemical (IHC) analysis of 154 EOC samples from two pooled, prospective, population-based cohorts. The hypotheses of the study were that PIGR expression would differ in relation to histological subtype,.