Ghrelin receptor as a novel imaging target for prostatic neoplasms.

BACKGROUND: Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed. METHODS: A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1-18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features. RESULTS: The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue. CONCLUSION: The imaging probe fluorescein-ghrelin(1-18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease.

Biopsy-derived Gleason artifact and prostate volume: experience using ten samples in larger prostates.

PURPOSE: To verify whether a significant relationship between the risk of Gleason upgrading and the prostate volume remains when the number of biopsies is increased for larger prostate volumes. MATERIALS: A total of 281 biopsy-proven prostate adenocarcinoma cases who underwent radical prostatectomy (RRP) formed the cohort for this study. Change in transrectal ultrasound of the prostate (TRUS) biopsies number based on total gland volume was made simply by increasing the number of biopsies from 6 to 10 when prostate volume was >50 cc. The total number of cancers with Gleason pattern 4 or greater on biopsy and on RRP was tabulated over TRUS volume categories and tests for trend. RESULTS: The proportion of Gleason score (GS) > or =7 at biopsy was 44.5% whereas, at RRP, it was 68.3%. The rate of upgrading from Gleason <7 at biopsy to GS > or =7 at RRP was 46.8%. No significant difference in terms of age, serum PSA, prostate volume and pT stage was found between not upgraded and upgraded cases (p > 0.05). As prostate volume categories increase, the number of cancers upgraded at RRP slightly increases in particular from prostate volume 30-39 to 40-49 cc (where only 6 biopsies were performed). However, either at biopsy or at RRP, the percentage of GS > or =7 tumors does not show a significant trend in changing (p > 0.05). CONCLUSIONS: We verified that the relationship between the risk of Gleason upgrading and prostate volume does not become significant simply by increasing the number of laterally directed biopsies from 6 to 10.

Long-term experience with an anatomical anterograde approach to radical prostatectomy: results in terms of positive margin rate.

PURPOSE: To evaluate the effect of an anterograde approach to radical retropubic prostatectomy (RRP) in terms of positive surgical margins (SM+). METHODS: 323 untreated patients underwent anterograde RRP for clinically localized prostate adenocarcinoma. Spearman coefficients, logistic univariate and multivariate analysis were used. RESULTS: The incidence of SM+ was 14.9% and, in particular, this was 4.5% for apical, 9.0% for lateral, 0.9% for other sites, and 2.8% for multiple SM+. Upon univariate analysis, prostate-specific antigen (PSA; r = 0.2073, p = 0.0002), pathological stage (r = 0.3777, p < 0.0001), and seminal vesicle invasion (r = 0.1453, p = 0.0089) were found to be significantly associated with SM+. Upon multivariate analysis, only PSA (p = 0.0090) and pathological stage (p < 0.0001) were significantly and independently associated with SM+ occurrence. CONCLUSION: In our experience, the anterograde approach to RRP is associated with low SM+ rates.

Comparison of chromogranin A, insulin-like growth factor 1 and prostate-specific antigen serum markers in prostate adenocarcinoma and benign prostatic hyperplasia.

BACKGROUND/AIM: To compare serum chromogranin A (CgA) and insulin-like growth factor 1 (IGF-1) with the classical prostate-specific antigen (PSA) marker in clinically localized prostate adenocarcinomas. MATERIALS AND METHODS: This is a prospective single-center study that included 64 consecutive men with newly diagnosed clinically localized prostate adenocarcinoma and 20 consecutive men with histologically confirmed benign prostatic hyperplasia (BPH). A blood sample for the determination of serum total PSA, CgA and IGF-1 levels (RIA) was obtained from all cases. Analysis of variance was performed to evaluate their variations according to disease and the pathological characteristics of prostate adenocarcinoma. RESULTS: Only serum PSA levels (p < 0.0001) and not IGF-1 (p = 0.5475) or CgA (p = 0.5043) were significantly higher in the prostate cancer (PCa) group as compared to the BPH group. A significant variance between BPH and PCa divided on the basis of pT stage was found for PSA levels (p < 0.0001) but not for CgA (p = 0.0869) and IGF-1 (p = 0.6883) levels. Dividing PCa on the basis of Gleason score, a significant variance was found for CgA (p = 0.0100) and for PSA (p < 0.001), but not for IGF-1 (p = 0.6895) levels. CONCLUSIONS: In our population the quantification of PSA and CgA serum levels and not of IGF-1 provides independent significant information in the diagnosis and aggressiveness of PCa, respectively.

Chromogranin A expression in familial versus sporadic prostate cancer.

OBJECTIVES: To evaluate whether a significant difference in chromogranin A (CgA) levels exist between patients with familial and sporadic cancer. METHODS: The study included 146 patients with clinically localized prostate adenocarcinoma (Stage T2N0M0), who underwent radical prostatectomy between June 1999 and June 2004. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first-degree relative (brother or father). On the day of surgery, a blood sample for the determination of serum prostate-specific antigen and CgA levels (radioimmunoassay) was obtained from all patients. In a subgroup of 20 patients, CgA mRNA expression was also evaluated by reverse transcriptase-polymerase chain reaction at the prostatic tissue level. RESULTS: A positive familial history was found in 28 (19.2%) of the 146 patients. The mean patient age in the familial group was significantly (P < 0.0001) lower than that in the sporadic group. No significant difference between the familial and sporadic groups was found in terms of prostate-specific antigen level (P = 0.9625) or Gleason score distribution (P = 0.4891). The familial group had significantly (P = 0.0013) lower serum CgA levels (43.3 +/- 12.7 ng/mL, median 39.9) compared with the sporadic group (55.9 +/- 19.4 ng/mL, median 54.1). The familial group also had significantly (P = 0.0432) lower expression of tissue CgA mRNA compared with the sporadic group. CONCLUSIONS: The result of significantly lower CgA expression in familial compared with sporadic prostate cancer cases suggests that neuroendocrine activity is not increased in familial cases and also confirms that familial cancer is not a more aggressive disease.