endothelin-1 and Prostatic-Intraepithelial-Neoplasia

To analyze the expression of endothelin-1 (ET-1), endothelin-A receptor (ET-A-R), and endothelin-B receptor (ET-B-R) in incidental prostate cancer in cystoprostatectomies (CyPs), clinically detected hormonally untreated and hormonally treated prostate cancer in radical prostatectomies (RPs), and hormone-independent prostate cancer in transurethral resections of the prostate (TURPs). High-grade prostatic intraepithelial neoplasia (HGPIN) was also investigated.. Nineteen CyPs and 44 RPs (25 untreated, 19 treated) with pT2a Gleason score 6 cancer and HGPIN were examined. The study included 9 TURPs with hormone-independent cancer and 8 normal cases from CyPs without prostate cancer and HGPIN. ET-1, ET-A-R, ET-B-R, and the proliferation marker Ki67 were investigated immunohistochemically.. The mean proportion of prostate cancer cells with strong ET-1, ET-A-R, and ET-B-R expression in CyPs was lower (18.5%, 28.0%, and 14.7%, respectively) than in the untreated group (40.7%, 39.7%, and 25.1%) and higher than in treated group (5.0%, 13.9%, and 11.3%). The highest values were in the hormone-independent cancer group (53.9%, 48.9%, 33.3%). The trend in the proportion of HGPIN cells overexpressing ET-1, ET-A-R, and ET-B-R was similar to that in the cancer groups. The values in HGPIN lesions were always slightly greater than those in the cancers. Ki67 expression in HGPIN and prostate cancer in CyPs was lower than in RPs and TURPs.. Our study showed for the first time that ET-1, ET-A-R, and ET-B-R expression is not limited to the late prostate cancer phases. It is also seen in HGPIN as well as in prostate cancers considered to be clinically insignificant, such as those seen in CyP specimens. Although the series of cases in each group was small, our data may have clinical significance.

Topics: Adult; Aged; Aged, 80 and over; Endothelin-1; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Receptor, Endothelin A; Receptor, Endothelin B

Topics: Endothelin-1; Humans; Male; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Receptor, Endothelin A; Receptor, Endothelin B

Emerging evidence supports a role for endothelin-1 (ET-1), endothelin A and B receptors (ET(A) and ET(B), respectively), and neutral endopeptidase (NEP) in the progression of prostate carcinoma. In clinical trials for advanced prostate cancer, ET axis blockade significantly delayed the time to disease progression in a subset of patients. We examined ET axis expression in prostate cancer, prostatic intraepithelial neoplasia, and normal adjacent tissue and then analyzed the relationship of the protein levels with disease progression.. The expression levels of ET(A), ET(B), and NEP were determined in 120 prostate cancer specimens obtained at surgery or biopsy by immunohistochemistry. In situ hybridization on a subset of the specimens was used to confirm the immunohistochemistry findings.. In regions of adenocarcinoma, immunohistochemistry analysis demonstrated high ET(A) expression in 72% of the specimens. ET(A) expression was significantly elevated with increased pathologic stage and grade. ET(B) and NEP levels were significantly decreased in adenocarcinoma compared with normal adjacent tissue and prostatic intraepithelial neoplasia; however, reduced expression did not correlate with tumor grade or stage. Patients with prostate-specific antigen recurrence had significantly greater ET(A) levels in their primary tumors than did patients who were disease free 5 years after prostatectomy. Patients with high ET(A) expression in the adenocarcinoma regions with low ET(B) and NEP had a significantly decreased interval to prostate-specific antigen progression compared with patients with low ET(A) or high ET(B)/NEP expression.. These data suggest two patterns of ET(A) expression in primary prostate cancer, with increased expression correlating with more advanced disease. The use of these expression patterns to identify patients more likely to respond to ET axis blockade might enhance treatment outcomes.

Topics: Aged; Aged, 80 and over; Endothelin-1; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Receptor, Endothelin A; Receptor, Endothelin B