Premium
MAGI2 is an independent predictor of biochemical recurrence in prostate cancer
Author(s) -
David Stephanie N.,
Arnold Egloff Shanna A.,
Goyal Rajen,
Clark Peter E.,
Phillips Sharon,
Gellert Lan L.,
Hameed Omar,
Giannico Giovanna A.
Publication year - 2018
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23506
Subject(s) - medicine , prostate cancer , prostatectomy , biochemical recurrence , tissue microarray , high grade prostatic intraepithelial neoplasia , intraepithelial neoplasia , urology , pten , cancer , oncology , prostate , breakpoint cluster region , pathology , biology , pi3k/akt/mtor pathway , receptor , signal transduction , biochemistry
Background Membrane‐associated guanylate kinase, WW and PDZ domain‐containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. Methods Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology. Results MAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, −0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880‐0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%). Conclusions These results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post‐operative surveillance intervals.