Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma.

ABSTRACT

INTRODUCTION: The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. MATERIALS AND METHODS: Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n = 173), including paired samples of benign-appearing squamous epithelium (n = 51), gastric mucosa (n = 114), Barrett's esophagus (BE) or intestinal metaplasia (IM) (n = 57) and lymph node metastases (n = 75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. RESULTS: PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p < 0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p = 0.002) and inversely associated with involved margins (p = 0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a prolonged OS (HR = 0.60, 95% CI 0.36-0.99) and RFS (HR = 0.49, 95% CI 0.27-0.90) in patients with radically resected (R0) primary tumours and of an improved RFS (HR = 0.32, 95% CI 0.15-0.69) in curatively treated patients with R0 resection/distant metastasis-free disease. CONCLUSION: High PIGR expression independently predicts a decreased risk of recurrence and an improved survival in patients with adenocarcinoma of the upper gastrointestinal tract. These findings are of potential clinical relevance and merit further validation.