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Samaratunga H.,Aquesta Pathology | Duffy D.,Queensland Institute of Medical Research | Yaxley J.,Royal Brisbane Hospital | Delahunt B.,University of Otago
Human Pathology | Year: 2010

Ductal adenocarcinoma of the prostate is an aggressive malignancy, often presenting at an advanced stage. In mixed ductal and acinar adenocarcinomas, the relationship between the proportion of the ductal component of the tumor and the pathologic stage and whether or not aggressive behavior is simply a function of grade remains undetermined. From 268 consecutive radical prostatectomies undertaken as a curative procedure for clinical localized prostate cancer, we identified 34 cases (12.7%) with ductal adenocarcinoma of the prostate comprising 5% to 100% of the total tumor volume. For cases with a ductal adenocarcinoma of the prostate component, the mean age at diagnosis of 60 years (range 49-69 years), mean serum prostate-specific antigen of 8.4 ng/mL (range, 0.8-21 ng/mL) and positive surgical margin rate of 17.6% did not differ significantly from that of the pure adenocarcinoma group. All 34 patients with ductal adenocarcinoma of the prostate had peripheral zone involvement while 16 (46%) also had transition zone involvement. Twenty-five (73%) cases with ductal adenocarcinoma of the prostate had extraprostatic extension (pT3), which compared to 32.9% with acinar adenocarcinoma. The presence of ductal adenocarcinoma of the prostate (P < .0001), high tumor volume (P = .001) and Gleason score >7 (P = .04) significantly predicted pT3 staging category, and the presence of ductal adenocarcinoma of the prostate remained a significant predictor for pT3, after adjusting for tumor volume and Gleason score >7. The proportion of ductal adenocarcinoma of the prostate did not significantly modify the strength of the observed association with pathological stage. In view of the significant association with extraprostatic extension we would recommend that in both core biopsies and radical prostatectomy specimens any proportion of ductal adenocarcinoma of the prostate should be reported. © 2010 Elsevier Inc.

Samaratunga H.,Aquesta Pathology | Samaratunga H.,University of Queensland | Martignoni G.,University of Verona | Egevad L.,Karolinska Institutet | Delahunt B.,University of Otago
Pathology | Year: 2013

Although most carcinomas of the bladder occur de novo, some vesical lesions progress to malignancy over time. These lesions appear morphologically benign, but often harbour genetic changes that signify their malignant potential. Despite their benign appearance, accurate identification is important given that these patients will require close followup. In addition to this some lesions may mimic carcinoma, and as a consequence, misdiagnosis could result in serious over-treatment. In this review, we discuss the clinical and histological features as well as the differential diagnosis of lesions of the bladder that have the potential to progress to cancer. Specifically, we present the features of flat, papillary and atypical urothelial hyperplasia, urothelial papilloma, urothelial dysplasia, intestinal metaplasia, keratinising squamous metaplasia, verrucous squamous hyperplasia and condyloma acuminatum and examine the molecular and clinical evidence relating to their malignant potential. © 2013 Royal College of Pathologists of Australasia.

Seipel A.H.,Karolinska Institutet | Samaratunga H.,Aquesta Pathology | Delahunt B.,University of Otago | Wiklund P.,Karolinska Institutet | And 2 more authors.
APMIS | Year: 2016

Ductal adenocarcinoma of the prostate (DAC) has morphological similarities to adenocarcinomas of other organs. DAC behaves in an aggressive manner and may present with metastases. These metastases may occur at unusual sites, which itself may cause diagnostic difficulties. It is important for therapeutic decisions that a prostatic origin of these metastases be established. Our aim was to compare the protein expression of DAC and adenocarcinomas of colon, endometrium, lung, pancreas, stomach and urinary bladder. A tissue microarray was constructed using 60 DAC, 6 colonic, 7 endometrial, 7 lung, 5 pancreatic, 5 gastric, and 9 urinary bladder adenocarcinomas. Slides were stained for estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c-Myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, and PAX-8. Androgen receptor, prostein, PSA, and PSAP were almost invariably expressed in DAC. Ki-67-labeling index was lower in DAC than in other adenocarcinomas. The expression patterns of intestinal markers and cytokeratins in DAC were less specific and may lead to diagnostic errors if not combined with prostate-specific markers. © 2016 APMIS Published by John Wiley & Sons Ltd.

Scott S.,Griffith University | Samaratunga H.,Aquesta Pathology | Samaratunga H.,University of Queensland | Chabert C.,Wesley Hospital | And 2 more authors.
BJU International | Year: 2015

Objectives To assess the degree of upgrading and increase in clinical risk category of transperineal template biopsy (TTB) compared with transrectal ultrasonography-guided prostate biopsy (TRUSB). Upgrading of TRUSB Gleason grade and sum after radical prostatectomy (RP) is well recognised. TTB may offer a more thorough mapping of the prostate than TRUSB, as well as a more accurate assessment of the tumour. In this retrospective cohort study of prospectively collected data, we compare the initial TRUSB and TTB Gleason grade and sum with the final assessment at RP. Patients and Methods Following Ethics Committee approval, 431 laparoscopic and robotic RP specimens of two urologists, fellowship-trained in minimally invasive RP, were examined in the private sector between April 2009 and October 2013. Final RP Gleason grade and sum were compared with the initial prostate biopsy. All pathological assessments were performed by a dedicated uropathology unit, experienced in prostate pathology. Upgrading was defined either as an increase in the primary Gleason grade, or as identification of a higher grade tertiary pattern at final RP analysis. Increase in clinical risk category was defined as an increase from low- (Gleason ≤6), to either intermediate- (Gleason 7) or high-risk disease (Gleason 8-10); or as an increase from intermediate- to high-risk disease. The chi-squared test was used to compare categorical variables, while the Wilcoxon rank sum was used for continuous quantitative variables. Results The 431 RP specimens comprised 283 in which the prostate cancer was diagnosed at TRUSB and 148 diagnosed at TTB. There was no difference between TRUSB and TTB in mean prostate weight (46.4 vs 44.2 g), final RP pathological stage (pT2: 187 vs 102; pT3 97 vs 48; P = 0.65) or mean tumour volume (2.15 vs 2.14 mL). Overall, 33.22% of TRUSB and 30.41% of TTB were upgraded, which was not significantly different (P = 0.55). Similarly there was no difference in whether there was an increase to a higher Gleason sum (TRUSB 23.3% vs TTB 20.9%; P = 0.57). TTB was more reflective of the actual clinical risk category, with TRUSB more likely to show an increase in clinical risk (TRUSB 22.3% vs TTB 14.2%; P = 0.04). Conclusions In this series, TTB more accurately predicted clinical risk category than TRUSB. TTB should be considered before active surveillance, to ensure that occult higher risk disease has not been under diagnosed. Upgrading and increase in clinical risk category was relatively common in each group highlighting the need for improved pretreatment staging accuracy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Bennett N.C.,University of Queensland | Hooper J.D.,Materials Medical Research Institute | Lambie D.,Princess Alexandra Hospital | Lee C.S.,University of Western Sydney | And 7 more authors.
American Journal of Pathology | Year: 2012

Malignant prostate cancer (PCa) is usually treated with androgen deprivation therapies (ADTs). Recurrent PCa is resistant to ADT. This research investigated whether PCa can potentially produce androgens de novo, making them androgen self-sufficient. Steroidogenic enzymes required for androgen synthesis from cholesterol (CYP11A1, CYP17A1, HSD3β, HSD17β3) were investigated in human primary PCa (n = 90), lymph node metastases (LNMs; n = 8), and benign prostatic hyperplasia (BPH; n = 6) with the use of IHC. Six prostate cell lines were investigated for mRNA and protein for steroidogenic enzymes and for endogenous synthesis of testosterone and 5α-dihydrotestosterone. All enzymes were identified in PCa, LNMs, BPH, and cell lines. CYP11A1 (rate-limiting enzyme) was expressed in cancerous and noncancerous prostate glands. CYP11A1, CYP17A1, HSD3β, and HSD17β3 were identified, respectively, in 78%, 52%, 16%, and 82% of human BPH and PCa samples. Approximately 10% of primary PCa, LNMs, and BPH expressed all four enzymes simultaneously. CYP11A1 expression was stable, CYP17A1 increased, and HSD3β and HSD17β3 decreased with disease progression. CYP17A1 expression was significantly correlated with CYP11A1 (P = 0.0009), HSD3β (P = 0.0297), and HSD17β3 (P = 0.0090) in vivo, suggesting CYP17A1 has a key role in prostatic steroidogenesis similar to testis and adrenal roles. In vitro, all cell lines expressed mRNA for all enzymes. Protein was not always detectable; however, all cell lines synthesized androgen from cholesterol. The results indicate that monitoring steroidogenic metabolites in patients with PCa may provide useful information for therapy intervention. © 2012 American Society for Investigative Pathology.

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