title: MAGI-2 in prostate cancer: an immunohistochemical study.
abstract: 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 3 tissue microarrays consisting of 512 cores, including benign tissue, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma, Gleason patterns 3 to 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 with benign (benign versus HGPIN P < .001; benign versus adenocarcinoma, P < .001). HGPIN and adenocarcinoma did not significantly differ by either modality. Using visual intensity to distinguish benign tissue and adenocarcinoma, a receiver operating 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 benign prostatic hyperplasia, but this was lost in HGPIN and cancer. We conclude that MAGI-2 immunoreactivity is elevated in prostate cancer and HGPIN compared with normal tissue, and suggest that MAGI-2 may contribute to prostate carcinogenesis. This is the first report of MAGI-2 staining by immunohistochemistry in prostate cancer.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: ja.goldstein@vanderbilt.edu.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Goldstein
authors.affiliation: 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. Electronic address: adborowsky@ucdavis.edu.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: rajen.goyal@gmail.com.
authors.forename: Rajen
authors.initials: R
authors.lastname: Goyal
authors.affiliation: Epithelial Biology Center, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: joseph.t.roland@vanderbilt.edu.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Roland
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232; Department of Veterans Affairs, Nashville, TN 37212. Electronic address: shanna.arnold@vanderbilt.edu.
authors.forename: Shanna A
authors.initials: SA
authors.lastname: Arnold
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: lan.gellert@vanderbilt.edu.
authors.forename: Lan L
authors.initials: LL
authors.lastname: Gellert
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: peter.clark@vanderbilt.edu.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232; Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: omar.hameed@vanderbilt.edu.
authors.forename: Omar
authors.initials: O
authors.lastname: Hameed
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address: giovanna.giannico@vanderbilt.edu.
authors.forename: Giovanna A
authors.initials: GA
authors.lastname: Giannico
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D002352:Carrier Proteins / Q000032:analysis*; D051528:Guanylate Kinases; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics; D011237:Predictive Value of Tests; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D012372:ROC Curve; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Image analysis; Immunohistochemistry; MAGI-2; PTEN; Prostate cancer