Immunoexpression of LGR4 and Β-Catenin in Gastric Cancer and Normal Gastric Mucosa

Abstract

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