Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) in prostate cancer: an immunohistochemical study

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) is a scaffolding protein that links cell adhesion molecules, receptors and signaling molecules to the cytoskeleton and maintains the architecture of cell junctions.

MAGI-2 gene rearrangements have recently been described in prostate cancer. We studied the immunohistochemical expression of MAGI-2 protein in prostate tissue. Seventy-eight radical prostatectomies were used to construct three tissue microarrays consisting of 512 1-mm cores, including benign tissue, benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma, Gleason patterns 3-5. Immunohistochemistry for phosphatase and tensin homologue (PTEN) and double stain MAGI-2/p63 was performed and analyzed by visual and image analysis, the latter as percent of analyzed area (%AREA), and mean optical density multiplied by %AREA (STAIN). By visual and image analysis MAGI-2 was significantly higher in adenocarcinoma and HGPIN compared to benign (benign vs. HGPIN p<0.001; benign vs. adenocarcinoma, p<0.001). HGPIN and adenocarcinoma did not significantly differ by either modality. Using visual intensity to distinguish benign and adenocarcinoma, a receiver/operator curve yielded an area under the curve of 0.902. A STAIN threshold of 1470 yielded a sensitivity of 0.66 and specificity of 0.96. There was a significant correlation between PTEN and MAGI-2 staining for normal and BPH, but this was lost in HGPIN and cancer. We conclude that MAGI-2 immunoreactivity is elevated in prostate cancer and HGPIN compared to normal, and suggest that MAGI-2 may contribute to prostate carcinogenesis. This is the first report of MAGI-2 staining by immunohistochemistry in prostate cancer.

Human pathology. 2016 Feb 04 [Epub ahead of print]

Jeffery Goldstein, Alexander D Borowsky, Rajen Goyal, Joseph T Roland, Shanna Arnold, Lan L Gellert, Peter E Clark, Omar Hameed, Giovanna A Giannico

Department of Pathology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Immunology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232.  Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Center for Comparative Medicine and Comprehensive Cancer Center, University of California Davis, Davis, CA 95616. Department of Pathology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Immunology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232. Department of Surgery, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232. Department of Pathology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Immunology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Veterans Affairs, 1310 24th Avenue South, Nashville, TN 37212.  Department of Pathology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Immunology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232. Department of Urologic Surgery, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232. Department of Pathology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Immunology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Urologic Surgery, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232. Department of Pathology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Microbiology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232; Department of Immunology, 1161 21st Ave. S., Vanderbilt University Medical Center, Nashville, TN 37232. 

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