Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinomaReport as inadecuate




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Journal of Translational Medicine

, 12:83

Disease Biomarkers

Abstract

IntroductionThe 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 methodsImmunohistochemical 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.

ResultsPIGR 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.

ConclusionHigh 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.

KeywordsPolymeric immunoglobulin receptor Esophageal adenocarcinoma Gastric adenocarcinoma Gastroesophageal junction adenocarcinoma Barrett’s esophagus Intestinal metaplasia Prognosis AbbreviationsTMATissue microarray

CRTClassification regression tree

PIGRPolymeric immunoglobulin receptor

BEBarrett’s esophagus

IMIntestinal metaplasia

HCCHepatocellular carcinoma

OSOverall survival

RFSRecurrence free survival

HRHazard ratio

IHCImmunohistochemistry

GEJGastroesophageal junction

ACAdenocarcinoma

PMNPolymorphonuclear neutrophil

SCSecretory component

IgAImmunoglobulin A, IL-8, interleukin 8

MMP-2Matrix metalloproteinase-2.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-83 contains supplementary material, which is available to authorized users.

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Author: Richard Fristedt - Alexander Gaber - Charlotta Hedner - Björn Nodin - Mathias Uhlén - Jakob Eberhard - Karin Jirström

Source: https://link.springer.com/







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