INTRODUCTION:Active surveillance (AS) has emerged as a primary management strategy for low-risk prostate cancer (PC) patients. We aimed to assess AS uptake over a 1-year snapshot throughout Quebec and to compare it to 2010 multicentric Canadian data.METHODS:A retrospective chart review and data collection was performed in 1 academic and 2 non-academic community centres from Quebec, among men identified in 2016 with localized T1c-T2c PC on biopsy, fulfilling NCCN criteria of low-risk (LR)-PC, including very-low-risk (VLR) and non-VLR-PC, and favourable-intermediate risk (FIR)-PC. AS adherence was defined when chosen as initial strategy, without any radical treatment within 6 months.RESULTS:Overall, 259 patients fulfilled the inclusion criteria with 50.2% of VLR-PC patients. At 6 months, 81% patients in the LR group and 65% in the FIR group were considered as adherent to AS, in both centres, but with an increased use of AS in the community centres compared to 2010 data. The rates of AS maintenance decreased at 12 months to respectively 69% and 58%. Among the VLR group, the rate of initiation was 98% and decreased to 85% at 12 months.CONCLUSION:Our data suggest that the majority of low-risk PC patients indeed initiated an AS in 2016, with even a greater proportion of VLR-PC patients compared to 2010. This ideal strategy should be encouraged and improved at 12 months, and assessed with recent data and longer follow-up.LEVEL OF EVIDENCE: 4:

Supplementary Materials and Methods, Supplementary Table, Supplementary References and Supplementary Figures S1 to S5

Supplementary Materials and Methods. Table S1: List of the different oligonucleotides used for mouse genotyping. Table S2: Phenotypic evaluation of prostate-specific PTP1B-overexpressing mice. Figure S1: Ptpn1 status does not alter the transition to mPIN in PtenPE-/- mice. Figure S2: Examples of mild and moderate desmoplasia. Figure S3: HFD drives invasive prostate cancer in the AP only in absence of Ptpn1. Figure S4: Ptpn1 status does not modulate mPIN formation in PtenPE+/- mice. Figure S5: Ptpn1 status influences PtenPE-/- phenotype in a dose-dependent manner.

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2017PD65-12 THE ANDROGEN RECEPTOR BECOMES A NOVEL PREDICTIVE BIOMARKER OF PROSTATE CANCER PROGRESSION WHEN POST TRANSLATIONALLY ACTIVATED BY THE FER KINASE ON TYROSINE 223 Turki Altaylouni, Fatima Zouanat, Eleonora Scarlata, Tarik Benidir, Lucie Hamel, Fadi Brimo, Louis Bégin, Armen Aprikian, and Simone Chevalier Turki AltaylouniTurki Altaylouni More articles by this author , Fatima ZouanatFatima Zouanat More articles by this author , Eleonora ScarlataEleonora Scarlata More articles by this author , Tarik BenidirTarik Benidir More articles by this author , Lucie HamelLucie Hamel More articles by this author , Fadi BrimoFadi Brimo More articles by this author , Louis BéginLouis Bégin More articles by this author , Armen AprikianArmen Aprikian More articles by this author , and Simone ChevalierSimone Chevalier More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2962AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is a leading cause of cancer deaths in USA. There is no cure for advanced disease; patients failing surgery or radiations invariably fail androgen-deprivation therapy (ADT) and further progress once castrate-resistant (CRPC). Studies point to anomalies in the androgen/androgen receptor (AR) axis in advanced PCa. We reported on the Fer tyrosine kinase directly activating AR on Y223 in PCa cells and becoming its partner in the tumor cell nucleus of CRPC patients (Rocha et al 2013). We aimed to assess the pY223AR fate in PCa. METHODS Sections of human prostate tissues and metastases were stained using pY223AR antibodies (Abs) we raised, and N- and C- terminal Abs to detect all AR forms vs wild-type, respectively. Results were expressed in percentages (%) and H scores. The cohort included 450 cases ranging from healthy men to benign hyperplasia, prostatectomies, neo-adjuvant hormone therapy, advanced on ADT, primary/lymph nodes, bone metastases and seminal vesicles. RESULTS AR and pY223AR-negative tumor cells constituted up to 15% in ADT/CRPC cases. In AR positive epithelial cells of normal and benign cases, the AR staining was mainly nuclear but negative for pY223AR. In primary tumors, the AR intensity and H scores increased with Gleason (p<0.01), being most elevated in ADT/CRPC. A shift in intensity from 1+ to +3 and +2 was observed with progression when all forms of AR were detected, whereas wild-type nuclear AR remained at 1+. Similar observations were made for all forms and wild-type AR in seminal vesicles, lymph nodes and bone metastases. Nuclear AR levels (all forms and wild-type) did not correlate with patient outcome. The nuclear intensity and H score of pY223AR also increased with Gleason of primary tumors (p<0.01), being most elevated in ADT/CRPC. Again, the pY223AR shifted from 1+ to +3 and +2 in the cell nucleus of primary tumors and metastases. Of interest, nuclear pY223AR correlated with biochemical recurrence (BCR) (Kaplan-Meier; log rank, p<0.0001 at H score=160). In univariate and multivariate analyses, pY223AR H scores predicted BCR (p<0.0001), PCa specific death (p=0.002) and overall survival (p=0.0002), independently of Gleason, stage and PSA. Also, combining pY223AR H score with PSA, GS and stages improved prognostication (ROC curves). CONCLUSIONS These findings suggest that activation of Y223 in all forms of AR is key for progression. Also, pY223AR represents a novel biomarker predicting outcome of prostate cancer. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1270-e1271 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Turki Altaylouni More articles by this author Fatima Zouanat More articles by this author Eleonora Scarlata More articles by this author Tarik Benidir More articles by this author Lucie Hamel More articles by this author Fadi Brimo More articles by this author Louis Bégin More articles by this author Armen Aprikian More articles by this author Simone Chevalier More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract Specific diets can affect the risk and progression of prostate cancer (PCa). However, the interplay between diet and genetic alterations remains ill defined. Here we show that progression of PCa that is driven by Pten loss is mostly unresponsive to a high fat diet; however, in the absence of protein tyrosine phosphatase Ptpn1 (which encodes PTP1B) mice that are fed a high fat diet develop a highly invasive disease that is characterized by increased cell proliferation and Akt activation. Together with the finding that prostate-specific PTP1B overexpression does not initiate PCa by itself, we conclude that PTP1B act as an environment-dependent tumor suppressor in the context of Pten-null prostate tumors. PTP1B is a validated therapeutic target at the crossroad of metabolism (diabetes, obesity) and cancer (breast), and is currently being investigated in clinical trials. Due to PTP1B's nutrient sensing capabilities, we suggest that a careful monitoring of the balance between improving metabolic syndrome and promoting oncogenic effects under particular diets be pursued when using PTP1B-targeted therapeutics. Citation Format: David P. Labbé, Noriko Uetani, Valérie Vinette, Isabelle Aubry, Eva Migon, Jacinthe Sirois, Jody J. Haigh, Laurent Lessard, Louis R. Bégin, Lloyd C. Trotman, Marilène Paquet, Michel L. Tremblay. PTP1B deficiency potentiate prostate cancer invasiveness by sensitizing Pten-null tumors to high-fat diet. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B39.

Background: SPINK1, ERG, and PTEN are proposed prognostic biomarkers in prostate cancer (PCA). However, their relations and patterns of expression in primary and metastatic lymph node (LN) PCAs are not fully explored.Methods: A tissue microarray of matched primary PCA and LN metastasis was constructed from 36 patients. SPINK1, ERG, and PTEN expression statuses were assessed by immunohistochemistry and correlated with each other.Results: SPINK1 and ERG were expressed in 25% and 42.7% of primary PCA cases, respectively. PTEN loss of any degree was observed in 91.7% of primary PCA cases, with 54.2% showing complete loss. In primary PCA, 12.5% of the cases showed SPINK1+/ ERG-phenotype, 16.7% showed SPINK1+/ERG+ phenotype, 25.0% showed SPINK1-/ERG+ phenotype, and 45.8% showed SPINK1-/ERG-phenotype. All PCAs with expression of either SPINK1 or ERG also exhibited PTEN loss, whereas PCA without PTEN loss (2 cases) expressed neither SPINK1 nor ERG. In primary PCA, evaluation of combined ERG and SPINK1 status, but not SPINK1 individually, was associated with a significant difference in proportion of Gleason patterns (P = 0.013), with the SPINK1+/ ERG+ and SPINK1-/ERG-phenotypes represented more in Gleason pattern >7 PCAs. In LN metastases, the overall SPINK1 protein expression frequency was significantly lower (6.5% of cases) compared with primary PCA (P = 0.03). Only 16.7% of cases with positive SPINK1 expression in primary PCA maintained expression in LN metastases. The down-regulated SPINK1 expression in LN was primarily because of a reduction in the SPINK1+/ERG+ PCA subpopulation to 3.5% of cases (P = 0.16 compared with primary PCA). The frequencies of ERG expression and PTEN loss were relatively stable in primary PCA and LN metastases.Conclusion: SPINK1 expression is dynamically regulated with up-regulation in primary sites of nodal metastatic PCA and down-regulation in LN metastases. The increased SPINK1 expression in primary site of nodal metastatic PCA is secondary to an increased frequency of SPINK1+/ERG+ tumors. In primary PCAs, the SPINK1+/ERG+ phenotype is associated with higher Gleason grade, suggesting that this phenotype may mark a more aggressive PCA subpopulation with higher risk of LN metastases. (C) 2016 Elsevier Inc. All rights reserved.

OBJECTIVE:To evaluate the clinical and pathological factors influencing the risk of disease progression in a cohort of patients with low-intermediate risk prostate cancer under active surveillance (AS). PATIENTS AND METHODS:We studied 300 patients diagnosed between 1992 and 2012 with prostate adenocarcinoma with favourable parameters or who refused treatment and were managed with AS. Of those, 155 patients with at least one repeat biopsy and no progression criteria at the time of the diagnosis were included for statistical analyses. Patients were followed every 3-6 months for prostate-specific antigen (PSA) measurement and physical examination. Patients were offered repeat prostatic biopsy every year. Disease progression was defined as the presence of one or more of the following criteria: ≥ 3 positive cores, >50% of cancer in at least one core, and a predominant Gleason pattern of 4. RESULTS:For the 155 patients, the mean (sd) age at diagnosis was 67(7) years; the median (interquartile range) follow-up was 5.4(3.6-9.5) years. Of these, 67, 25, six, and two patients had two, three, four, and five repeat biopsies, respectively. At baseline, 11 (7%) patients had a Gleason score of 3+4, while the remaining 144 (93%) patients had a Gleason score of ≤ 6. In all, 50 (32.3%) patients had disease progression on repeat biopsies, with a median progression-free survival time of 7 years. The rate of disease progression decreased after the second repeat biopsy. The 5-year overall survival rate was 100%. Having a PSA density (PSAD) of >0.15 ng/mL/mL, >1 positive core, and Gleason score >6 at the time of the diagnosis was associated with a significantly higher rate of disease progression on univariate analysis (P < 0.05), while a maximum percentage of cancer in any core of >10% showed a trend toward significance for a higher progression rate (P = 0.054). On multivariate analysis, only the presence of a PSAD of >0.15 ng/mL/mL remained significant for a higher progression rate (P < 0.05). Of the 155 patients, five (3.2%) subsequently received radiotherapy, 13 (8.4%) received hormonal therapy, and 13 (8.4%) underwent radical prostatectomy. CONCLUSION:AS is a suitable management option for patients with clinically low-risk prostate cancer. A PSAD of >0.15 ng/mL/mL is an important predictor for disease progression.

INTRODUCTION:While RARP (robotic-assisted radical prostatectomy) has become the predominant surgical approach to treat localized prostate cancer, there is little Canadian data on its oncological and functional outcomes. We describe the largest RARP experience in Canada.METHODS:Data from 722 patients who underwent RARP performed by 7 surgeons (AEH performed 288, TH 69, JBL 23, SB 17, HW 15, QT 7, and KCZ 303 patients) were collected prospectively from October 2006 to December 2013. Preoperative characteristics, as well as postoperative surgical and pathological outcomes, were collected. Functional and oncological outcomes were also assessed up to 72 months postoperative.RESULTS:The median follow-up (Q1-Q3) was 18 months (9-36). The D'Amico risk stratification distribution was 31% low, 58% intermediate and 11% high-risk. The median operative time was 178 minutes (142-205), blood loss was 200 mL (150-300) and the postoperative hospital stay was 1 day (1-23). The transfusion rate was only 1.0%. There were 0.7% major (Clavien III-IV) and 10.1% minor (Clavien I-II) postoperative complications, with no mortality. Pathologically, 445 men (70%) were stage pT2, of which 81 (18%) had a positive surgical margin (PSM). In addition, 189 patients (30%) were stage pT3 and 87 (46%) with PSM. Urinary continence (0-pads/day) returned at 3, 6, and 12 months for 68%, 80%, and 90% of patients, respectively. Overall, the potency rates (successful penetration) for all men at 6, 12, and 24 months were 37%, 52%, and 59%, respectively. Biochemical recurrence was observed in 28 patients (4.9%), and 14 patients (2.4%) were referred for early salvage radiotherapy. In total, 49 patients (8.4%) underwent radio-therapy and/or hormonal therapy.CONCLUSIONS:This study shows similar results compared to other high-volume RARP programs. Being the largest RARP experience in Canada, we report that RARP is safe with acceptable oncologic outcomes in a Canadian setting.

Background. A 51-year-old French Canadian man presented to his family physician owing to an extensive family history of prostate cancer in five brothers, his father and two paternal uncles. His serum PSA level was 4.9 ng/ml and a six-core biopsy revealed the presence of a prostate adenocarcinoma with a Gleason score of 7 (3+4). He was treated with radical prostatectomy. Repeat PSA tests revealed a gradual rise in PSA levels despite androgen deprivation therapy with bicalutamide and goserelin over the course of 3 years. Genetic evaluation was undertaken in view of his personal and family history. The proband died at the age of 58 years of widespread metastasis.Investigations. PSA testing, six-core biopsy, genetic counselling and mutation analysis for French Canadian founder mutations in the BRCA1 and BRCA2 genes, histopathological review of tumour tissue from family members, examination of loss of heterozygosity at the BRCA2 gene locus, immunohistochemistry to determine the expression of the ERG nuclear oncoprotein in prostate tumours, genotyping with eight selected risk-associated single nucleotide polymorphisms, Doppler ultrasonography of the leg, CT of the abdomen and pelvis with intravenous and oral contrast, chest CT with intravenous contrast for the assessment of metastatic prostate cancer, genetic testing for the G84E variant in the HOXB13 gene.Diagnosis. Early-onset and aggressive prostate cancer associated with a nonsense French Canadian BRCA2 founder mutation, c.5857G>T (p.Glu1953*).Management. Radical prostatectomy, hormone therapy with bicalutamide and goserelin, palliative chemotherapy initially with docetaxel plus prednisone then with mitoxantrone plus prednisone, as well as genetic counselling and testing for the proband and his family members.

PURPOSE:Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.EXPERIMENTAL DESIGN:A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.RESULTS:We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.CONCLUSIONS:Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.

This chapter provides a contemporary pathobiological perspective on various aspects of prostate cancer relating to diagnosis, phenotypical characterization, and prognostication. The emphasis is on conventional adenocarcinoma whose incidence has increased dramatically in the last two decades as a result of serum PSA screening. Following a brief histological overview of the normal prostate, the gross, microscopic, and immunophenotypical features of adenocarcinoma are described, including tumoral variants that can mimic benign conditions on biopsy assessment. In-depth discussion of the Gleason grading system is provided as it has a major impact on prognostic determination and treatment options. Taking into account recent modifications resulting from the 2005 ISUP Consensus Conference, the spectrum of histopathological patterns (grades) and methodology applied to biopsy or surgical specimens to obtain a Gleason score are described. Issues such as tumor quantification, extraprostatic extension (EPE), seminal vesicle invasion, surgical margin (SM) status and pelvic lymph node involvement are covered in terms of stringent definition and prognostic relevance. Cancer-related iatrogenic changes resulting from radiation therapy and androgen-deprivation therapy are outlined. Their recognition having an impact on patient management, entities such as high-grade prostatic intraepithelial neoplasia (HGPIN) (an accepted precursor lesion of many adenocarcinomas) and the descriptive designation of atypical small acinar proliferation (ASAP) are discussed. Accounting for no more than 5–10% of prostate cancer, we briefly describe the special subtypes of tumor, such as ductal adenocarcinoma, urothelial carcinoma, and small cell carcinoma, among others. Emerging biomarkers of potential prognostic interest are selectively and briefly outlined.

BackgroundImmunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype.Methods and findingsWe pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy.ConclusionsThe six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required.

Most neoplasms of the testis are of germ cell origin. More than half of germ cell tumors contain more than one histologic type and are referred to as malignant mixed germ cell tumors. The American Cancer Society estimates that 8,400 new cases of testicular germ cell tumors will be diagnosed in 2009 in the United States (American Cancer Society. http://www.cancer.org). The incidence varies by country and socioeconomic status and ranges from one to ten per 100,000 (Eble et al. 2004) with the highest incidence in developed European countries such as Germany, Denmark, Norway, and Switzerland (Ferlay et al. 2001). The incidence of testicular germ cell tumors, specifically, seminoma has been increasing in populations of European descent (Coleman et al. 1993). There is speculation that the increased incidence in developed countries is related to a high-fat western diet and lack of physical activity associated with higher socioeconomic status. Due to advances in treatment, the overall 5-year survival rate for testicular germ cell tumors is 96% and is even greater for localized disease (American Cancer Society. http://www.cancer.org). This chapter deals exclusively with adult germ cell tumors; however, excellent reviews of pediatric germ cell tumors are available elsewhere (Wojno and Bloom 1997).

A 59-year-old woman was referred for evaluation of shortness of breath. Physical examination was remarkable for a faint apical mid-diastolic murmur. Transthoracic echocardiography (TTE) demonstrated moderate rheumatic mitral valve stenosis with valve area of 1.3 cm 2 by both planimetry and pressure half time. A mass lesion with a broad base was seen attached to the interatrial septum (IAS) inside the left atrium (Fig. 1, Movie 1). Transoesophageal echocardiography (TEE) revealed that the mass (23 x 33 mm) was encapsulated, heterogeneous with cystic degeneration, attached with a broad base to the lower portion of the IAS and extended to the anterior mitral leaflet consistent with left atrial myxoma (LAM). The mass was fixed and did not show any independent mobility or sliding through the mitral valve orifice (Fig. 2, Movie 2). Colour Doppler echocardiography showed that the mass was partially vascularized (Fig. 3, Movie 3). Coronary angiography ruled out significant coronary artery disease and uncovered atypical vascularization of the mass from both right and left coronary arteries (Movies 4 and 5). Cardiovascular magnetic resonance imaging was consistent with LAM. The patient was referred for cardiac surgery. The mass was excised, followed by mitral valve replacement due to encroachment on the anterior mitral leaflet. Gross appearance and histology showed typical features of myxoma (Figs. 4 and 5). The discrimination between LAM and atrial thrombi presents a diagnostic challenge in the presence of mitral stenosis. Usually, LAM arises from the IAS at the level of fossa ovalis. Atrial thrombi classically reside in an atrial appendage, but can also form in the LA body.

Aims:BRCA1-related breast cancer is associated with a basal-like phenotype, and is frequently oestrogen receptor (ER) and HER2 negative. The expression of epidermal growth factor receptor (EGFR) has been considered to be one component of the basal-like phenotype, but no standard criteria exist. This study investigates the relationship between EGFR expression, BRCA1 status and basal markers with respect to clinicopathological associations and prognosis, in addition to evaluating different criteria for EGFR assessment by immunohistochemistry.Methods:A tissue microarray comprising 230 available cases, from a series of primary invasive breast cancer diagnosed in Ashkenazi Jewish women during 1980–1995, was stained for EGFR using the Dako PharmDX kit, and evaluated by Webslide virtual microscopy.Results:EGFR was positive in 9–19% according to different criteria. Expression was associated with BRCA1 carrier status and basal-like markers as negative ER, positive cytokeratin 5/6 and positive P-cadherin staining. EGFR was prognostically significant by univariate and multivariate analysis within the group carrying germ-line BRCA1 mutations. Histological grade, axillary lymph node status and P-cadherin status had significant independent value in the final multivariate model including all cases, whereas EGFR was not significant in this model. All five scoring systems gave comparable results concerning clinicopathological associations and patient outcome, although the most restrictive criteria (EGFR-HI) tended to be most sensitive in predicting BRCA1 status, a basal phenotype, and patient prognosis.Conclusions:EGFR expression, being present in 9–19% of the cases, was prognostically significant among BRCA1 mutated cases only. In multivariate survival analysis of all cases, no independent effect was seen. However, EGFR immunostaining might be relevant to predict the response to targeted therapy, and this should be studied further.

Purpose Several retrospective studies, including our previous investigation, have shown a prognostic value of nuclear shape factor in colorectal carcinomas. This prospective study was designed to assess the reliability of nuclear shape factor determined by nuclear morphometry and to confirm its prognostic value. Methods Ninety-eight patients who underwent colorectal carcinoma resection were prospectively enrolled. Measurement of nuclear shape factor was performed by using a computer-based image analysis system. Nuclear shape factor was defined as the degree of circularity of the nucleus (1.0 for a perfect circle and <1.0 for any other elliptical shape). The prognostic impact of nuclear shape factor on ten-year survival and the intraobserver and interobserver agreement were assessed. Results The nuclear shape factor mean values by American Joint Committee on Cancer stage were: 0.73 (0.07) in Stage I, 0.74 (0.06) in Stage II, and 0.75 (0.05) in Stage III carcinomas ( P = 0.78, ANOVA). The intraobserver agreement was poor for observer A ( r = 0.28) and practically nonexistent for observer B ( r = −0.004, Pearson correlation). The intraclass coefficient for interobserver agreement was practically nonexistent. No significant association between nuclear shape factor and ten-year survival was found. Conclusions Our prospective results, as opposed to our previous retrospective results, suggest that the reliability for nuclear shape factor morphometric analysis is very poor. We failed to confirm a prognostic value for nuclear shape factor in colorectal carcinoma.

Background. Microsatellite instability (MSI) is a form of genomic instability that has recently been implicated in the pathogenesis of thyroid cancer. The purpose of this study was to further define the distribution of MSI in both normal and neoplastic thyroid follicular epithelium.Design. Using laser capture microdissection, cells from both normal and tumor tissue were individually collected. Polymerase chain reaction amplification of the DNA was then performed using six dinucleotide and two mononucleotide microsatellite markers.Results. Forty benign and malignant thyroid tumors were compared with their adjacent normal thyroid follicular tissue and were analyzed for MSI. Nine of 14 papillary thyroid carcinomas and 10/16 of follicular thyroid carcinomas demonstrated MSI at >= 30-40% of loci tested. For benign follicular adenomas, 9/10 demonstrated microsatellite stability or low-frequency MSI.Conclusion. MSI appears to play a role in thyroid pathogenesis as evidenced by the high frequency of MSI in malignant thyroid neoplasms. In addition our study showed a significant difference in MSI frequency between follicular adenomas and follicular carcinomas. More importantly, the technique of laser capture microdissection allows for more accurate selection of benign, malignant, and normal DNA. (c) 2008 Elsevier Inc. All rights reserved.

You have accessJournal of Urology1 Apr 2008PATHOLOGIC DISEASE PROGRESSION ON REPEAT TRANSRECTAL BIOPSY IN A CONTEMPORARY WATCHFUL WAITING PROSTATE CANCER COHORT Andrew Feifer, Mohammed F Al-Otaibi, Kanishka Sircar, Louis R Begin, Armen G Aprikian, Wassim Kassouf, and Simon Tanguay Andrew FeiferAndrew Feifer More articles by this author , Mohammed F Al-OtaibiMohammed F Al-Otaibi More articles by this author , Kanishka SircarKanishka Sircar More articles by this author , Louis R BeginLouis R Begin More articles by this author , Armen G AprikianArmen G Aprikian More articles by this author , Wassim KassoufWassim Kassouf More articles by this author , and Simon TanguaySimon Tanguay More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)60567-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "PATHOLOGIC DISEASE PROGRESSION ON REPEAT TRANSRECTAL BIOPSY IN A CONTEMPORARY WATCHFUL WAITING PROSTATE CANCER COHORT." The Journal of Urology, 179(4S), pp. 195–196 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 195-196 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Andrew Feifer More articles by this author Mohammed F Al-Otaibi More articles by this author Kanishka Sircar More articles by this author Louis R Begin More articles by this author Armen G Aprikian More articles by this author Wassim Kassouf More articles by this author Simon Tanguay More articles by this author Expand All Advertisement PDF downloadLoading ...