Decreased RECK Expression Indicating Proteolytic Imbalance in Prostate Cancer is Associated with Higher Tumor Aggressiveness and Risk of Prostate-Specific Antigen Relapse after Radical Prostatectomy

Abstract Objectives Decreased expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) was recently shown in several cancer types. To evaluate its potential role for prostate carcinoma, we investigated RECK expression in prostate cancer (pCA) samples. Methods RECK messenger RNA levels in 15 microdissected normal/tumor matches were determined by quantitative reverse transcriptase-polymerase chain reaction. Protein expression of RECK was evaluated by immunohistochemical staining in tissue samples of adenomectomies ( n =24) and pCA samples after radical prostatectomy ( n =247). RECK expression was related to preoperative prostate-specific antigen (PSA), tumor stage and grade, surgical margin status, and PSA relapse-free time after radical prostatectomy. Results Consistent with lower RECK messenger RNA by 24%, RECK protein expression was decreased in pCA, compared with adjacent normal tissue and prostatic intraepithelial neoplasia. RECK expression in samples of benign prostatic hyperplasia from adenomectomy specimens was higher than in normal adjacent tissue of prostate carcinomas. Decreased RECK expression was associated with higher Gleason score (≥7) and higher tumor stage. Multivariate analysis using the Cox proportional hazards model revealed that negative RECK expression was an independent prognostic factor for an increased risk of PSA relapse, especially in patients with higher tumor grades (Gleason score ≥7). Conclusions Decreased RECK expression correlating with the aggressiveness of pCA and the PSA relapse-free time could become an adjunct tissue biomarker to improve the follow-up and treatment decision for these pCA patients.