Immunoexpression of LGR4 and B-catenin in gastric cancer and normal gastric mucosa

Abstract

Background: We evaluated the immunoexpression of LGR4 and β-catenin in primary gastric carcinomas, lymph node metastases and histologically normal gastric mucosa in the surgical margins of gastric primary tumours. Methods: We performed a cross-sectional, observational study, based on 75 gastric carcinoma specimens from gastrectomies conducted at the hospital of the Federal University of Ceará, Brazil. The samples were analysed by tissue microarray and immunohistochemistry. Chi-square, Fisher's exact test and Pearson's linear regression were used in this study. Results: LGR4 expression was greater in the histologically normal gastric mucosa (basal third of the epithelial thickness) of the tumour surgical resection margin than in the cases of primary carcinomas (P < 0.001, mainly diffuse-histotype cancer margins), and also in the number of cells stained in the normal mucosa (P < 0.0001). Primary intestinal-type carcinomas showed greater positivity for LGR4 than diffuse tumours (59% vs 13%, P < 0.0001) and in these the positivity was higher in the metastases (P=0.0242). The membranous immunoexpression of β-catenin was ubiquitous in the normal mucosa and present in 2/3 of the positive carcinomas. In only one case, nuclear β-catenin expression was observed. Most LGR4-positive cases were stained for membranous β-catenin but not the opposite (P < 0.01). Conclusion: LGR4 is a likely biomarker of stem cells in the normal gastric mucosa and carcinomas of the stomach, not specific to cancer cells and positively associated with cell proliferation. LGR4 immunoexpression is more frequent and found in a larger number of cells in normal tissues than in tumour samples. Expression of β-catenin in the junctional membrane-complex occurred predominantly, in positive cases of gastric carcinomas and very rarely in the nucleus. LGR4 apparently influenced the membranous expression of β-catenin. These findings suggest a controversial role for LGR4, related to proliferative status and inversely related to tumour progression, in contrast to most previous reports.