N-cadherin switching occurs in high Gleason grade prostate cancer

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Abstract
BACKGROUND The inappropriate expression of non-epithelial N-(neural) cadherin by epithelial cells, called cadherin switching, has been suggested to play a role in prostate cancer (PC) progression. We explored the role of N-cadherin as a biomarker in PC by correlating the expression with clinical parameters. METHODS Two pathologists blinded to patients' history independently reviewed and scored the intensity and extent of staining of N-cadherin expression in 44 randomly selected radical prostatectomy specimens. The expression was correlated with total Gleason grade, individual Gleason patterns, tumor stage, and preoperative serum prostate specific antigen (PSA) levels and P-values < 0.05 were considered statistically significant. RESULTS Of the 44 PC specimens, 14 (32%), 23 (52%), 7 (16%) consisted of Gleason grade 5–6, 7, and 8–10, respectively and 20/44 (45%) demonstrated N-cadherin expression. N-cadherin was expressed in 1/14 (7%) of Gleason 5–6 compared to 15/23 (65%) of Gleason grade 7, and 4/7 (57%) of Gleason grade 8–10, demonstrating a significant correlation between N-cadherin switching and higher Gleason grade (P = 0.001). While only about a third of primary or secondary Gleason pattern 3 demonstrated N-cadherin expression, a majority of Gleason patterns of ≥ 4 expressed N-cadherin (P > 0.05), further suggesting that N-cadherin switching occurs with higher Gleason pattern. However, N-cadherin expression did not significantly correlate with preoperative serum PSA levels or tumor stage in our study cohort. CONCLUSIONS We have demonstrated for the first time that N-cadherin switching occurs in higher grade PC and correlates significantly with increasing Gleason patterns. N-cadherin may be as a useful biomarker of aggressive PC.