The Role Of P501s And Psa In The Diagnosis Of Metastatic Adenocarcinoma Of The Prostate

[No abstract available]335723724Xu, J., Kalos, M., Stolk, J.A., Zasloff, E.J., Zhang, X., Houghton, R.I., Identification and characterization of prostein, a novel prostate-specific protein (2001) Cancer Res, 61, pp. 1563-1568Xu, J., Stolk, J.A., Zhang, X., Silva, S.J., Houghton, R.I., Matsumura, M., Identification of differentially expressed genes in human prostate cancer using subtraction and microarray (2000) Cancer Res, 60, pp. 1677-1682Zhou, M., Chinnaiyan, A.M., Kleer, C.G., Lucas, P.C., Rubin, M.A., Alpha-Methylacyl-CoA racemase: A novel tumor marker over-expressed in several human cancers and their precursor lesions (2002) Am J Surg Pathol, 26, pp. 926-93

Risk of prostate cancer after isolated high-grade prostatic intraepithelial neoplasia (HGPIN) detected on extended core needle biopsy : a UK hospital experience.

Background High-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor lesion to prostate cancer (CaP). UK-based studies examining the occurrence of isolated HGPIN and subsequent risk of CaP are lacking. Our aim was to assess the occurrence of HGPIN in a regional UK population and to determine whether in a retrievable cohort of such patients that had repeat extended core biopsies, there was an elevated risk of CaP. Methods A retrospective analysis of the pathology database was conducted at our institution (Lancashire Teaching Hospitals NHS Foundation Trust) for prostate biopsies recorded between January 2001 and December 2005 (all extended core biopsies). Those patients with isolated HGPIN on 1st set of biopsies were identified and, their clinical characteristics and pathological findings from subsequent biopsies (if any) were determined. The risk of CaP on subsequent biopsies based on presenting baseline PSA was stratified. Results Of 2,192 biopsied patients, there were 88 cases of isolated HGPIN of which 67 patients underwent one or more repeat biopsies. In this repeat-biopsy group, 28 CaP diagnoses were made. Age at first biopsy (P 20 ng/ml – 87.5%. Conclusion Based on our results, we recommend delaying the 1st repeat biopsy at low PSA range but to have a shorter interval to repeat biopsies at intermediate and higher PSA ranges

Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.

BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection

Human Gastric Mucosa Expresses Glandular M3 Subtype of Muscarinic Receptors

Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 ± 6 fmol/mg protein and the tritiated ligand N-methylscopolamine had an affinity of (Kn) 0.39 ± 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148 ± 32 nM (n = 13) and 4043 ± 1011 nM (n = 3) K n , respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities ofKn 78 ± 23 nM (n = 5) and 5.6 ± 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type

Periacinar retraction clefting and d2-40 expression in prostatic adenocarcinoma

Retraction clefting is known to appear in various types of tumors, but it has only recently been recognized as a specific histological phenomenon. Previously, it was considered merely a laboratory procedure artifact, but lately, there have been some assumptions that peritumoral retractions actually represent lymphatic spaces. In our study, we analyzed neoplastic glands in 52 specimens of prostatic adenocarcinoma. Immunohistochemical analysis was performed using D2-40 antibody, to highlight lymphatic endothelium and thereby differentiate actual lymph vessels or lymphovascular invasion from periacinar retractions. Our results showed that the number of lymph vessels was significantly lower in tumorous tissue compared to adjacent normal prostatic tissue. On the other hand, the number of lymph vessels in tumorous tissue was significantly higher than the number of lymph vessels mimicking periacinar retractions. Overall, the number of lymph vessels mimicking periacinar clefts was particularly low. These results are in accordance with our previous studies, which had shown that periacinar clefting appears due to lack of basal cells and stromal changes around tumorous acini. Also, these results support our hypothesis that retractions do not represent lymph vessels but should be considered a distinct entity, which is proven to be helpful both as diagnostic and predictive factor