Cell polarity protein Lgl2 is lost or aberrantly localized in gastric dysplasia and adenocarcinoma: an immunohistochemical study
Authors
Lisovsky, MikhailDresser, Karen A.
Baker, Stephen P.
Fisher, Andrew
Woda, Bruce A.
Banner, Barbara F.
Lauwers, Gregory Y.
UMass Chan Affiliations
Department of Cell BiologyInformation Services, Academic Computing Services
Department of Pathology
Document Type
Journal ArticlePublication Date
2009-05-02Keywords
AdenocarcinomaAdenoma
Adolescent
Adult
Aged
Aged, 80 and over
Cell Polarity
Cytoskeletal Proteins
Female
Fluorescent Antibody Technique, Direct
Gastric Mucosa
Humans
Immunoenzyme Techniques
Male
Middle Aged
Precancerous Conditions
Stomach Neoplasms
Tumor Markers, Biological
Young Adult
Life Sciences
Medicine and Health Sciences
Technology and Innovation
Metadata
Show full item recordAbstract
The diagnosis of gastric epithelial dysplasia, a precursor lesion of gastric adenocarcinoma, is hindered by interobserver variability and by its resemblance to regenerative changes. Loss of cell polarity, a histological feature of gastric epithelial dysplasia, may be difficult to ascertain, especially in the setting of inflammation or injury. A biomarker of cell polarity could be useful in diagnosis of dysplasia, but has not been reported. The Lethal giant larvae (lgl) gene controls apical-basal polarity of epithelial cells in Drosophila, and has properties of a tumor-suppressor gene. Two homologs, lgl1 and lgl2, are present in mammals and lgl2 mRNA is highly expressed in the stomach. The goal of our study was to test the hypothesis that Lgl2 protein expression and/or localization are disrupted in gastric epithelial dysplasia and adenocarcinoma. Routinely processed pathology specimens including 94 benign mucosae of digestive organs, in addition to 36 reactive gastropathy, 57 gastric epithelial dysplasia, and 77 gastric adenocarcinomas, were immunostained for Lgl2 protein. All normal, reactive, and chronically inflamed gastric epithelia showed basolateral Lgl2 staining. Normal esophageal, duodenal, colonic, biliary, and pancreatic duct mucosae, as well as gastric intestinal metaplasia, did not express Lgl2. All but one case each of gastric epithelial dysplasia and adenocarcinoma showed either complete loss of anti-Lgl2 immunoreactivity or diffuse, mostly weak, cytoplasmic staining. Complete loss of immunoreactivity was significantly more often observed in diffuse-type than in intestinal-type adenocarcinomas (79 vs 48%, respectively). Our data suggest that Lgl2 expression is either aberrantly localized or lost in gastric epithelial dysplasia and adenocarcinoma, whereas it is maintained in reactive gastric mucosa. We propose that Lgl2 may be a potential marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic specimens. However, the consistently negative anti-Lgl2 immunoreactivity seen in intestinal metaplasia does not allow differentiation of dysplasia from intestinal metaplasia with reactive change.Source
Mod Pathol. 2009 Jul;22(7):977-84. Epub 2009 May 1. Link to article on publisher's siteDOI
10.1038/modpathol.2009.68Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35340PubMed ID
19407852Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/modpathol.2009.68