Upregulation of Leukotriene Receptors in Gastric Cancer

Marino Venerito,Thomas Wex,Peter Malfertheiner,Caroline Harms,Doerthe Kuester,Daniel Schubert

doi:10.3390/cancers3033156

Abstract

BackgroundLeukotrienes (LT) mediate allergic and inflammatory processes. Previously, we identified significant changes in the expression pattern of LT receptors in the gastric mucosa after eradication of Helicobacter pylori infection. The aim of the present study was to evaluate the expression of 5-lipoxygenase (5-LOX) and LT receptors in gastric cancer (GC).MethodsThe expression of 5-LOX and receptors for LTB4 (BLT-1, BLT-2) and cysteinyl-LT (CysLT-1, CysLT-2) were analyzed by immunohistochemistry (IHC) in GC samples of 35 consecutive patients who underwent gastrectomy and in 29 tumor-free tissue specimens from gastric mucosa.ResultsMale-to-female ratio was 24:11. The median age was 70 years (range 34–91). Twenty-two patients had GC of intestinal, six of diffuse, six of mixed and one of undifferentiated type. The IHC analysis showed a nearly ubiquitous expression of studied proteins in GC (88–97%) and in tumor-free specimens as well (89–100%). An increase in the immunoreactive score of both BLT receptors and CysLT-1 was observed in GC compared to tumor-free gastric mucosa (p < 0.001 for BLT-1; p < 0.01 for BLT-2 and CysLT-1, Mann-Whitney U-test). No differences in the IHC expression of 5-LOX and CsyLT-2 were observed between GC and tumor-free mucosa. The expression of BLT-2, CysLT-1 and CysLT-2 was increased in GC of intestinal type when compared to the diffuse type (p < 0.05; Mann-Whitney U-test).ConclusionsLTB4 receptors and CysLT-1 are up-regulated in GC tissue implying a role in gastric carcinogenesis.

Highlights

Gastric cancer (GC) incidence has been rapidly declining in most Western countries [1]
LTB4 receptors and CysLT-1 are up-regulated in gastric cancer (GC) tissue implying a role in gastric carcinogenesis
The gastric surface and foveolar epithelium showed a medium to strong cytoplasmatic immunostaining for 5-LOX and CysLT-1 and a weak to medium expression pattern for BLT-1, BLT-2 and CysLT-2

Summary

Introduction

Gastric cancer (GC) incidence has been rapidly declining in most Western countries [1]. The decrease of GC incidence has been steady and well documented for decades [3,4,5], and reflects most likely the reduction of risk factors for GC, in particular changes in food preservation (cooling and freezing instead of salting, smoking and fermentation) and a decreasing prevalence of Helicobacter pylori (H. pylori) by birth cohort [3]. Despite this reduction in several regions, GC remains a clinical challenge and burden worldwide, individually and socio-economically. An increase in the immunoreactive score of both BLT receptors and

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