Abstract
BackgroundHigh expression of the polymeric immunoglobulin receptor (PIGR) has previously been associated with a favourable prognosis in a few cancer forms, but its expression and relationship with clinical outcome in epithelial ovarian cancer (EOC) has not yet been reported. The aim of this study was therefore to examine the clinicopathological correlates and prognostic significance of PIGR expression in EOC.MethodsAfter an initial screening in the Human Protein Atlas portal, a validated antibody was selected for extended analysis of immunohistochemical PIGR expression in tissue microarrays with tumours from 154 incident cases of EOC from two pooled prospective population-based cohorts. Subsets of corresponding benign-appearing fallopian 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).ResultsPIGR 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.ConclusionsThis 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.
Highlights
Epithelial ovarian cancer (EOC) is the fifth most common cancer type in women in more developed areas and the most lethal malignancy of the female reproductive tract [1]
polymeric immunoglobulin receptor (PIGR) expression was significantly higher in fallopian tubes compared to primary tumours (p = 0.0009) and to metastases (p = 0.0004, Figure 2)
As samples from all three locations were only available for six patients, this study did not allow for a meaningful analysis of PIGR expression related to individual tumour progression
Summary
Epithelial ovarian cancer (EOC) is the fifth most common cancer type in women 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]. 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. High expression of the polymeric immunoglobulin receptor (PIGR) has previously been associated with a favourable prognosis in a few cancer forms, but its expression and relationship with clinical outcome in epithelial ovarian cancer (EOC) has not yet been reported.
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