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Mount Waverley, Australia

Hong M.K.H.,Royal Melbourne Hospital | Hong M.K.H.,Australian Prostate Cancer Research Center | Yao H.H.I.,Royal Melbourne Hospital | Yao H.H.I.,Australian Prostate Cancer Research Center | And 12 more authors.
BJU International | Year: 2012

OBJECTIVE: • To evaluate the accuracy of calculated prostate volume variables in a radical prostatectomy (RP) cohort, as many recent studies use these measures of prostate size instead of prostate weight. • To determine whether this accuracy could be improved by modifying the mathematical model used in the volume estimation. PATIENTS AND METHODS: • Patients who underwent RP for prostate cancer at our associated institutions had calculated specimen volumes and weights from RP specimens determined at one pathology institution and transrectal ultrasonography (TRUS) volumes were recorded preoperatively ( n = 236). • Correlation analysis was performed and errors were determined for calculated volume variables when compared with prostate weight. • Bland-Altman plots were drawn and concordance coefficients calculated. • Analysis was repeated with smaller prostates mathematically modelled as bullet-shaped rather than ellipsoid ( n = 165). RESULTS: • Although correlation was good for both TRUS and specimen volumes, they equally underestimated prostate weight with a large range of errors and poor concordance coefficients. • Only 22% of TRUS volumes and 11% of calculated specimen volumes were within 10% of weight measurements. • Application of a bullet-shaped mathematical model for prostates < 55 g did not correct the large individual variation seen within these values. CONCLUSION: • Calculated prostate volume variables are prone to a large range of individual error regardless of the mathematical model used and should be avoided in statistical studies involving RP cohorts, and the more accurate prostate weight variable should instead be used as a size variable or correction factor. © 2012 The Authors.

Naeem H.,Victoria University of Melbourne | Naeem H.,University of Melbourne | Wong N.C.,Murdoch Childrens Research Institute | Wong N.C.,Ludwig Institute for Cancer Research | And 8 more authors.
BMC Genomics | Year: 2014

Background: The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA methylation of 485,512 CpGs in the human genome. The technology relies on hybridization of genomic fragments to probes on the chip. However, certain genomic factors may compromise the ability to measure methylation using the array such as single nucleotide polymorphisms (SNPs), small insertions and deletions (INDELs), repetitive DNA, and regions with reduced genomic complexity. Currently, there is no clear method or pipeline for determining which of the probes on the HM450K bead array should be retained for subsequent analysis in light of these issues.Results: We comprehensively assessed the effects of SNPs, INDELs, repeats and bisulfite induced reduced genomic complexity by comparing HM450K bead array results with whole genome bisulfite sequencing. We determined which CpG probes provided accurate or noisy signals. From this, we derived a set of high-quality probes that provide unadulterated measurements of DNA methylation.Conclusions: Our method significantly reduces the risk of false discoveries when using the HM450K bead array, while maximising the power of the array to detect methylation status genome-wide. Additionally, we demonstrate the utility of our method through extraction of biologically relevant epigenetic changes in prostate cancer. © 2014 Naeem et al.; licensee BioMed Central Ltd.

Fankhauser M.,Royal Melbourne Hospital | Tan Y.,Royal Melbourne Hospital | Macintyre G.,Victoria University of Melbourne | Haviv I.,Victoria University of Melbourne | And 10 more authors.
Clinical Cancer Research | Year: 2014

Purpose: It has been recognized for almost a decade that concentrations of signaling androgens sufficient to activate the androgen receptor are present in castration-resistant prostate cancer tissue. The source of these androgens is highly controversial, with three competing models proposed. We, therefore, wished to determine the androgenic potential of human benign and malignant (hormone-naïve and treated) prostate tissue when incubated with various precursors and examine concomitant changes in enzyme expression. Experimental Design: Freshly harvested prostate tissue [benign, hormone-naïve, and hormone-refractory prostate cancer (HRPC)] was incubated in excess concentrations of cholesterol, progesterone, DHEA, androstenedione, or testosterone for 96 hours, and steroid concentrations in the conditioned media measured by gas chromatography-mass spectroscopy. Changes in the expression of androgen synthetic and/or degradative enzymes were determined by expression microarray and qPCR. Significant changes were confirmed in an independent dataset. Results: Of the precursor molecules tested, only incubation with androstenedione gave rise to significant concentrations of signaling androgens. Although this was observed in all tissue types, it occurred to a significantly greater degree in hormone-refractory compared with hormone-naïve cancer. Consistent with this, gene set enrichment analysis of the expression microarray data revealed significant upregulation of 17HSD17B activity, with overexpression of the canonical enzyme AKR1C3 confirmed by qPCR in the same samples and in a publicly available expression dataset. Importantly, we found no evidence to support a significant contribution from either the "backdoor" or "5-α dione" pathway. Conclusions: Reduction of androstenedione to testosterone by the canonical HSD17B AKR1C3 is the predominant source of signaling androgens in HRPC. ©2014 AACR.

Durrani N.,Sir Charles Gardiner Hospital | Waldron M.,University of New England of Australia | Cherry C.,Burnet Institute | Cherry C.,University of Witwatersrand | And 4 more authors.
Open Prostate Cancer Journal | Year: 2015

Objectives: To determine whether assessing expression of MUC1 and ZAG proteins in prostate biopsies, by immunohistochemistry, improves prediction of radical prostatectomy histopathology, which in turn predicts longer-term outcomes. Methods: We studied 231 consecutive patients managed by two experienced urologic surgeons (MF, LH). Each patient had prostate biopsies revealing cancer followed by a radical prostatectomy. Expression of MUC1 and ZAG in biopsy tissue was assessed by immunohistochemistry, masked to the radical prostatectomy histopathology. Data were analysed by Chi-square, Fischer exact test & Mann Whitney U test followed by multivariate analysis using binary logistic regression. Results: By univariate analysis, MUC1 expression in prostate biopsies was associated with worse histopathology in the radical prostatectomy specimen (p<0.023), while ZAG expression was associated with better pathology (p=0.03). By multivariate analysis decreased expression of ZAG in biopsies (p=0.02), but not MUC1 expression, improved prediction of high-risk radical prostatectomy pathology beyond conventional biopsy variables; neither MUC1 nor ZAG staining improved prediction of minimal-risk cancers. Conclusions: Assessment of ZAG expression in prostate biopsies, and possibly MUC1 expression, may improve knowledge of prostate cancers in vivo or after radical prostatectomy. © Durrani et al.; Licensee Bentham Open.

Pedersen J.S.,TissuPath Specialist Pathology | Pedersen J.S.,Monash University | Clarke I.,Monash University | Mills J.,TissuPath Specialist Pathology | Mills J.,Monash University
Histopathology | Year: 2011

Aims: To develop an antibody broadly reactive against mycobacterial species, which will improve detection of mycobacteria in tissue sections by immunohistochemistry (IHC). Methods: A sheep antisera was developed by immunization with multiple mycobacteria, and was tested by IHC against a range of mycobacteria in tissues from many species, as well as negative tissue controls and other bacteria. Results: The sheep antiserum, MAS-01, reacted with all 18 mycobacterial species tested, but did not react with uninfected inflammatory tissues. Although MAS-01 cross-reacted with two microbial genera which are related to mycobacteria (Corynebacteria and Proprionibacteria), it did not with Nocardia or Actinomyces. The antibody was more sensitive than the Ziehl-Neelsen stain for detection of tissue mycobacteria, and shortened the time required to identify these infections. Conclusion: The MAS-01 antiserum will facilitate rapid identification of tissue mycobacterial infection by histopathologists. © 2011 Blackwell Publishing Limited.

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