Document Type: Research Articles
Department of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Ceará, Brazil.
Fortaleza Air Base, Aeronautics, Armed Forces, Brazil.
Postgraduate Program in Dentistry, Department of Dental Clinic, Federal University of Ceará,, Brazil.
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.