CD146 protein in prostate cancer: revisited with two different antibodies.

AIMS: CD146 is a potentially metastasis promoting cell adhesion molecule and its expression has been described in various solid tumours. We aimed to evaluate the expression of CD146 in prostate cancer by immunohistochemistry in a clinically characterised study cohort to evaluate its prognostic properties. METHODS: We evaluated the CD146 protein expression using a polyclonal and a monoclonal antibody on 169 clinico-pathologically characterised cases. Statistical analyses were applied to test for correlations and diagnostic and prognostic associations. RESULTS: CD146 detection with the polyclonal antibody revealed marked differential expression between tumour and normal tissue and was also a significant marker for shortened PSA relapse free survival. The monoclonal CD146 antibody demonstrated a weaker epithelial signal, which was significantly correlated with that of the polyclonal antibody, but revealed no prognostic value. However, the Western blot of the polyclonal antibody displayed a clearly reduced specificity. CONCLUSIONS: Evaluation of protein expression can be highly dependent on the primary antibody employed. A credible evaluation of antibody specificity is crucial to prove the validity of protein expression studies. The immunoreactivity of the polyclonal CD146 antibody (Abcam, ab28360) is prognostic of PSA-relapse in prostate cancer patients, although its immunoreactivity is possibly not restricted to CD146 associated epitopes.

ADAM8 expression in prostate cancer is associated with parameters of unfavorable prognosis.

Gene products of the A disintegrin and metalloprotease (ADAM) family are critically involved in carcinogenesis and tumor progression of various solid tumors. Little is known about ADAM8 in prostate cancer. In our quest for novel diagnostic tissue markers of prostate cancer, we aimed to evaluate the expression of ADAM8 in prostate cancer and to correlate it with clinicopathological parameters. One hundred twenty-eight clinicopathologically characterized prostate cancer patients, with available follow-up data, were immunostained for ADAM8. Additionally, ADAM8 mRNA expression was quantified by real-time reverse transcription polymerase chain reaction (n = 59). ADAM8 protein expression was significantly associated with higher pT status, positive nodal status, and higher Gleason scores. Still, a significant prognostic value for the prostate-specific antigen relapse-free survival of ADAM8 could not be demonstrated. The differentiality of ADAM8 expression on protein and on mRNA level was low and partially inconclusive. Therefore, despite of its significant association with conventional parameters of an unfavorable prognosis, ADAM8 adds only limited information to the conventional histopathological assessment of prostate cancer.

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.

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 (> or =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 > or =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.

Overexpression of cyclooxygenase-2 in human prostate carcinoma and prostatic intraepithelial neoplasia-association with increased expression of Polo-like kinase-1.

BACKGROUND: Cyclooxygenases (COX) as well as Polo-like kinases (PLK) are involved in proliferation and cell cycle regulation and have been suggested for preventive and therapeutic approaches in prostate carcinoma. METHODS: In this study, we studied expression and prognostic impact of COX-2 in invasive prostate carcinoma, prostatic intraepithelial neoplasia (PIN), atrophic glands, and normal prostatic glands, and investigated the association between COX-2 and PLK-1. RESULTS: We observed a positivity for COX-2 in 72.1% of PIN and in 44.7% of prostate carcinomas with an overexpression of COX-2 in prostate cancer and PIN compared to benign prostatic tissue (P < 0.0005). Furthermore, we observed a strong correlation between expression of PLK-1 and COX-2 (P < 0.0005). CONCLUSIONS: To our knowledge, this is the first report of a correlation between COX-2 and PLK-1 in a malignant tumor. COX-2 and PLK-1 may be interesting targets for new molecular therapies in prostate cancer.