Prostate Needle Core Biopsies Research Articles

Histologic findings on prostate needle core biopsies following cryotherapy as monotherapy for prostatic adenocarcinoma

The histologic features seen in the prostate following cryotherapy can be highly variable. However, most previous studies were performed on specimens following salvage cryotherapy, which introduces additional confounding variables of the histologic changes after the other primary treatment modalities. We examined prostate needle core biopsies from a cohort of patients following cryotherapy as monotherapy for prostatic adenocarcinoma, to evaluate the true spectrum of morphologic changes in the prostate. Cases that had prior radiation therapy or androgen-deprivation therapy were excluded from the study. Thirty cases were identified. The average patient age was 69 years (range, 51-81 years), and the average time interval between cryotherapy and repeat biopsy was 19.2 months (range, 2-60 months). The original Gleason scores were as follows: 3 + 3 = 6 in 14 (46%) of 30 cases, 3 + 4 = 7 in 8 (27%) of 30 cases, 4 + 3 = 7 in 2 (7%) of 30 cases, 4 + 4 = 8 in 3 (10%) of 30 cases, 4 + 5 = 9 in 2 (7%) of 30 cases, and 5 + 4 = 9 in 1 (3%) of 30 cases. Postcryotherapy, 11 of 30 cases (37%) had recurrent/residual prostatic adenocarcinoma, which showed no therapy-related changes, similar to the residual benign glands. Gleason scores were higher in 5 (46%) of 11 cases, same in 4 (36%) of 11 cases, and lower in 2 (18%) of 11 cases. Multiple additional histologic findings were documented. Unlike other nonsurgical therapeutic modalities, cases with recurrent/residual prostatic adenocarcinoma and benign glands showed therapy-related changes predominantly involving the stroma. It is therefore conceivable that benign or malignant prostatic glands are either completely destroyed during cryotherapy or left unaltered if not in the direct field of cryoablation.

The Number of Cores Taken in Patients Diagnosed with a Single Microfocus at Initial Biopsy is a Major Predictor of Insignificant Prostate Cancer

Patients with a single microfocus of prostate cancer at initial biopsy represent the ideal candidates for active surveillance. We investigate whether the number of cores taken affects the concordance rate between microfocus of prostate cancer and the confirmation of a pathologically insignificant prostate cancer at radical prostatectomy. Data were analyzed from 233 patients with a single microfocus of prostate cancer at initial transrectal prostate biopsy (a single focus of Gleason 6 involving 5% or less of the core) subsequently treated with radical prostatectomy. The chi-square test, cubic spline analyses and logistic regression analyses were used to depict the relationship between the number of cores taken and the probability of confirming the presence of an indolent disease (pathologically confirmed insignificant prostate cancer defined as radical prostatectomy Gleason score 6 or less, tumor volume 0.5 ml or less and organ confined disease). Overall 65 patients (27.9%) showed pathologically confirmed insignificant prostate cancer at radical prostatectomy. The rate of pathologically confirmed insignificant prostate cancer was 3.8%, 29.6% and 39.4% in patients who underwent biopsy of 12 or fewer cores, 13 to 18 cores and 19 or more cores, respectively (p <0.001). After adjusting for the available confounders, age (p = 0.04), number of cores taken (p <0.001) and prostate specific antigen density (p <0.02) were independent predictors of pathologically confirmed insignificant prostate cancer. Of patients diagnosed with a single microfocus of prostate cancer the number of biopsy cores taken was a major independent predictor of having pathologically confirmed insignificant prostate cancer at radical prostatectomy. Therefore, when active surveillance is considered as a possible alternative in patients with microfocus of prostate cancer, the number of cores taken should be taken into account in decision making.

Inflammation and preneoplastic lesions in benign prostate as risk factors for prostate cancer

AbstractBenign changes ranging from atrophy and inflammation to high-grade prostatic intraepithelial neoplasia (HGPIN) are common findings on prostate core needle biopsies. Although atrophy and inflammation may be precursors of prostate cancer, only HGPIN is currently recommended to be included in surgical pathology reports. To determine whether these benign findings increase prostate cancer risk, we conducted a case–control study nested within a historical cohort of 6692 men with a benign prostate specimen collected between 1990 and 2002. The analytic sample included 574 case–control pairs comprised of cases diagnosed with prostate cancer a minimum of 1 year after cohort entry and controls matched to cases on date and age at cohort entry, race, and type of specimen. The initial benign specimen was reviewed for presence of HGPIN, atrophy (simple, lobular, and partial) and inflammation (glandular and/or stromal). HGPIN significantly increased risk for prostate cancer (odds ratio (OR)=2.00; 95% confidence interval (CI)=1.25–3.20). Inflammation within the stromal compartment was associated with decreased risk (OR=0.66; CI=0.52–0.84), and diffuse stromal inflammation of severe grade had the strongest inverse association with risk (OR=0.21; CI=0.07–0.62). In a model adjusted for prostate-specific antigen (PSA) level at cohort entry and inflammation, simple atrophy was associated with a 33% increased prostate cancer risk that was marginally significant (P=0.03). Clinicians should consider patterns and extent of inflammation when managing high-risk patients with negative biopsy results. Identifying benign inflammatory processes that underlie high PSA levels would help to reduce the number of unnecessary repeated prostate biopsies.

A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection

BackgroundPSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence.ResultsAn initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP). The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE) samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 μm can be used to detect methylation in a reliable manner. The age of FFPE-samples does have a negative impact on DNA quality and quantity.ConclusionsThe developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples.

Castration Therapy of Prostate Cancer Results in Downregulation of HIF-1α Levels

Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1α (HIF-1α) in cancer was determined by immunofluorescence. Among biopsy specimens taken before castration, strong HIF-1α expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1α (mean intensity 0-10) in 6 patients. Downregulation of HIF-1α expression after castration was observed in all 5 patients with strong HIF-1α precastration expression. HIF-1α expression was also reduced in 2 of 3 patients with weak HIF-1α precastration expression. Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.

Identification of Gleason Pattern 5 on Prostatic Needle Core Biopsy: Frequency of Underdiagnosis and Relation to Morphology

Identification of Gleason Pattern 5 on Prostatic Needle Core Biopsy: Frequency of Underdiagnosis and Relation to Morphology

Touch imprint cytology of prostate core needle biopsy specimens: A useful method for immediate reporting of prostate cancer

Background:Cytology plays an important role in the preoperative assessment of many cancers. It is used as a first-line pathological investigation in both screening and diagnostic purposes.Aims:To determine the diagnostic value and accuracy of touch imprint cytology (TIC) smear of prostate core needle biopsy (CNB) specimens in the diagnosis of prostate carcinoma.Materials and Methods:One hundred and twenty-one patients had ultrasound-guided transrectal prostate CNB. A total of 1210 TIC smears were prepared from all CNB specimens.Results:Diagnoses of 1210 TIC smears were compared with the histopathological findings of the CNB specimens. One hundred and seventy (14%) TIC smears were found positive for malignancy, 35 (2.9%) were diagnosed as suspicious for malignancy and 1005 (83.1%) were found negative for malignancy. Twenty-five of 35 suspicious imprints and 150 of 170 malignant smears were confirmed to be malignant on histopathological evaluation. Although 20 malignant TIC smears were defined as benign in standard histological preparations, 10 of them had definitive diagnosis of malignancy following extensive serial sectioning. Last of all, there were 10 false-positive cytology results. Moreover, 10 of the 35 suspected TIC smears were false negative when compared with the histopathological diagnosis. The sensitivity, specificity, positive predictive value and negative predictive value of touch imprint smear results were 100%, 98%, 90.2% and 100%, respectively.Conclusions:TIC smears can provide an immediate and reliable cytological diagnosis of prostate carcinoma. It may clearly help the rapid detection of carcinoma, particularly in highly suspected cases that had negative routine biopsy results for malignancy with abnormal serum prostate specific antigen (PSA) levels and atypical digital rectal examination.

Identification of Gleason pattern 5 on prostatic needle core biopsy: frequency of underdiagnosis and relation to morphology

Abstract The presence of a Gleason pattern 5 prostatic adenocarcinoma is associated with a worse outcome. This study assesses the accuracy of grading a tumor as having Gleason pattern 5 and the potential factors contributing to its undergrading. From the consultation service of one of the authors, we identified 59 consecutive needle biopsy cases comprising 138 parts that, upon review, were graded as having Gleason pattern 5. All cases were reported as the final diagnosis by the outside pathologist. They were sent for a second opinion at the behest of clinicians or patients and not because the pathologist was seeking a second opinion. Considering the highest Gleason score in a given multicore specimen as the overall Gleason score, Gleason pattern 5 was missed in 34 of 59 (57.6%) cases by the outside pathologist. Compared with the outside pathologist's diagnosis, the Gleason score rendered at the second opinion was increased in 101 of 138 (73.2%) parts, was decreased in 5 of 138 (3.6%) parts, and remained unchanged in 32 of 138 (23.2%) parts. Gleason pattern 5 was not identified by the initiating pathologist in 67 of 138 (48.6%) of the evaluated parts. The architectural patterns of pattern 5 were as follows: single cells (n=104, 75.3%); solid sheets (n=69, 50%); cords (n=62, 44.9%); and comedonecrosis (n=3, 2.2%). Pattern 5 was missed more frequently when it was not the primary pattern. The most common Gleason pattern 5 architectural type was single cells and the least common was comedonecrosis. None of the architectural patterns appeared to be more correctly identified than the others; however, the most accurate grading was when the primary pattern was 5 and was composed mostly of solid sheets. Owing to the important prognostic and therapeutic implications of Gleason pattern 5, pathologists must be attuned to its varied patterns and to the fact that it may often represent a secondary or tertiary component of the carcinoma.

Identification of Gleason Pattern 5 on Prostatic Needle Core Biopsy

The presence of a Gleason pattern 5 prostatic adenocarcinoma is associated with a worse outcome. This study assesses the accuracy of grading a tumor as having Gleason pattern 5 and the potential factors contributing to its undergrading. From the consultation service of one of the authors, we identified 59 consecutive needle biopsy cases comprising 138 parts that, upon review, were graded as having Gleason pattern 5. All cases were reported as the final diagnosis by the outside pathologist. They were sent for a second opinion at the behest of clinicians or patients and not because the pathologist was seeking a second opinion. Considering the highest Gleason score in a given multicore specimen as the overall Gleason score, Gleason pattern 5 was missed in 34 of 59 (57.6%) cases by the outside pathologist. Compared with the outside pathologist's diagnosis, the Gleason score rendered at the second opinion was increased in 101 of 138 (73.2%) parts, was decreased in 5 of 138 (3.6%) parts, and remained unchanged in 32 of 138 (23.2%) parts. Gleason pattern 5 was not identified by the initiating pathologist in 67 of 138 (48.6%) of the evaluated parts. The architectural patterns of pattern 5 were as follows: single cells (n=104, 75.3%); solid sheets (n=69, 50%); cords (n=62, 44.9%); and comedonecrosis (n=3, 2.2%). Pattern 5 was missed more frequently when it was not the primary pattern. The most common Gleason pattern 5 architectural type was single cells and the least common was comedonecrosis. None of the architectural patterns appeared to be more correctly identified than the others; however, the most accurate grading was when the primary pattern was 5 and was composed mostly of solid sheets. Owing to the important prognostic and therapeutic implications of Gleason pattern 5, pathologists must be attuned to its varied patterns and to the fact that it may often represent a secondary or tertiary component of the carcinoma.

Gleason Pattern 5 is Frequently Underdiagnosed on Prostate Needle-core Biopsy

To assess underdiagnosing Gleason pattern 5 on needle biopsy and discuss the potential consequences for patient management. We retrieved 300 consecutive prostate biopsy cases from the consultation files at The Johns Hopkins Hospital (JHH) from 2009-2010 in which we identified Gleason pattern 5. All of these cases were diagnosed by one of the authors and all were sent in as a final diagnosis for which the outside pathologist was not requesting consultation because of difficulty with the diagnosis. The Gleason grades assigned to these cases at our institution were compared with the grade rendered by the submitting pathologists from the outside institution. In 146 (48.7%) of the cases, Gleason pattern 5 was not identified by the outside pathologists. Of the 146 cases, the outside Gleason score was ≤7 in 61 (20.3%) and 4+4=8 in 85 (28.4%). Even when the tumor was diagnosed at JHH as Gleason score 5+5=10, only 26 (41.3%) were diagnosed as the same by the outside pathologists; Gleason score 9 was graded in 27 (42.8%). Considering the important prognostic and therapeutic implication of misdiagnosing Gleason pattern 5, efforts should be made by the pathology community to acknowledge this as a problem and improve on individual pathologists' accuracy by diverse medical education programs. In addition, urologists should not hesitate in sending biopsies with high-grade prostate cancer for expert genitourinary pathology second opinions.

Evaluation of metastatic potential of prostate cancer

We aimed to establish a method for evaluating malignant potential of prostate cancer using prostatic core needle biopsy (PCNB) before prostatectomy. If we can know the final pathological stage before treatment, we can select the most suitable therapeutic tactics. We then examined the expression of E-cadherin and type IV collagenase (MMP-9/-2), which play essential role in cancer cell invasion and metastasis. The expression ratio of MMP-9/-2 to E-cadherin (MER) is revealed as the relevant marker correlated with the final pathological stage and Gleason score by prostatectomy specimens. We next confirmed the significance of MER in PCNB, which means PCNB MER enables the prediction of the final pathologic stage at the cancer diagnosis. However, the methodology measuring MER is complicated to produce an observer-to-observer deviation. We then establish a bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector- based system. By this method, we can reduce an observer-to-observer deviation and a slide-to-slide deviation. The bicolor FISH-based MER is a useful tool for the preoperative evaluation of the final pathologic stage, by which we can assure a decision of prostatectomy indication.

Evaluation of metastatic potential of prostate cancer

We aimed to establish a method for evaluating malignant potential of prostate cancer using prostatic core needle biopsy (PCNB) before prostatectomy. If we can know the final pathological stage before treatment, we can select the most suitable therapeutic tactics. We then examined the expression of E-cadherin and type IV collagenase (MMP-9/-2), which play essential role in cancer cell invasion and metastasis. The expression ratio of MMP-9/-2 to E-cadherin (MER) is revealed as the relevant marker correlated with the final pathological stage and Gleason score by prostatectomy specimens. We next confirmed the significance of MER in PCNB, which means PCNB MER enables the prediction of the final pathologic stage at the cancer diagnosis. However, the methodology measuring MER is complicated to produce an observer-to-observer deviation. We then establish a bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector- based system. By this method, we can reduce an observer-to-observer deviation and a slide-to-slide deviation. The bicolor FISH-based MER is a useful tool for the preoperative evaluation of the final pathologic stage, by which we can assure a decision of prostatectomy indication.

Prostate needle biopsy examination by means of virtual microscopy

This study aimed at determining whether virtual microscopy improves the accuracy in the pathological examination of prostate needle biopsies regarding maximum tumor length, percentage of positive cores, and Gleason grading. We assessed a series of 816 prostate needle biopsy cores in 68 consecutive patients with prostate adenocarcinoma. Biopsy specimens were reviewed using conventional examination. Then, slides were converted to whole slide imaging (Olympus BX51). Tumor was measured, and Gleason score was assigned using the OlyVia software. Optically evaluated pathological features were compared with digital findings to determine whether one of these two methods for the assignment of a preoperative Gleason score is appropriate for predicting the definitive Gleason score of radical prostatectomy. When comparing optical and digital measurements, maximum tumor length in biopsy cores and percent prostate needle biopsy with cancer showed no significant difference. The mean variation in the measurement of tumor length was 2.65 mm per biopsy. Among 240 biopsy cores involved with cancer, the concordance rate for Gleason score assignment was 75.8% ( κ = 0.49, good agreement). When considering the higher Gleason score assignment as the score for the entire case (ISUP 2005), the concordance rate was 69.1% ( κ = 0.46, good agreement). When comparing the biopsy scores with the definitive score of radical prostatectomy, the concordance rate was significantly increased from 54.4% for conventional examination ( κ = 0.23, marginal agreement) to 66.2% for virtual slide examination ( κ = 0.42, good agreement). Virtual microscopy does not compromise, but might improve, the accuracy of grading in prostate needle biopsies. This requires further assessment.

Tissue print of prostate biopsy: a novel tool in the diagnostic procedure of prostate cancer

BackgroundNowadays, the histological examination of prostate core needle biopsies is still regarded as the gold standard in the diagnosis of prostate cancer (PCa). We investigated if the tissue print of core needle biopsy (biopsy print) could be used as adjunctive molecular investigative procedures in conjunction with routine histological examination of biopsy to improve PCa diagnosis.MethodsThe direct contact of PCa core biopsy to nitrocellulose membrane resulted in the release of a cellular micropeel that was used for downstream analytical procedures.ResultsBy zymogram print-phoresis we demonstrated that matrix metalloproteases MMP-2 and MMP-9 could be visualized in biopsy prints and that the gelatinolytic activity was positively correlated with immunohistochemistry analysis of the same markers in matched bioptic specimens. Moreover, we compared the ability to detect the PCa-associated hypermethylation of GSTP1 promoter in DNA extracted from biopsy prints with those of the corresponding core needle biopsies. Biopsy prints demonstrated the same specificity of biopsies in detecting PCa (50%) while the sensitivity and the positive predictive value were lower than biopsies (56% vs 78% and 63% vs 70%, respectively).ConclusionsBiopsy print, combining a molecular point of view to the routinely hystopathological analysis of prostate biopsies, should be a useful tool to improve the diagnosis of PCa.

186 PROSTATE NEEDLE BIOPSIES: HISTOPATHOLOGY AND METABOLITE BIOMARKERS ON THE SAME TISSUE BIOPSY

You have accessJournal of UrologyProstate Cancer: Staging1 Apr 2011186 PROSTATE NEEDLE BIOPSIES: HISTOPATHOLOGY AND METABOLITE BIOMARKERS ON THE SAME TISSUE BIOPSY Dean Troyer, Raymond Lance, Klaus-Peter Adam, Danny Alexander, and Jeffrey Shuster Dean TroyerDean Troyer Norfolk, VA More articles by this author , Raymond LanceRaymond Lance Norfolk, VA More articles by this author , Klaus-Peter AdamKlaus-Peter Adam Durham, NC More articles by this author , Danny AlexanderDanny Alexander Durham, NC More articles by this author , and Jeffrey ShusterJeffrey Shuster Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.256AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate needle biopsies are the gold standard for prostate cancer diagnosis. Biopsies are analyzed by hematoxylin and eosin (H&E) histopathology for diagnosis, and for cancer aggressiveness by Gleason grade. Gleason grade is reported as a semi-quantitative, categorical variable. Small molecule metabolite biomarkers, for which measurements are more quantitative, are also useful in the determination of the aggressiveness of prostate cancer (Sreekumar et al., Nature, 457:910, 2009). These assays routinely require extraction methods which disrupt tissue architecture and, as such, preclude measuring metabolites and performing histology on the same portion of tissue. We present a new method which allows both histology and metabolomics to be performed on exactly the same tissue biopsy. The method is compatible with existing clinical and histology workflows. METHODS Prostatectomy specimens were biopsied ex vivo, and placed in an alcohol-based fixative. The biopsies were then removed from the alcohol fixative, processed, embedded in paraffin, sectioned, and stained by standard methods. The alcohol was retained and analyzed by metabolomics using a mass spectrometry-based platform (Evans et al., Anal. Chem. 81:6656–67, 2009). RESULTS The figure below shows prostate needle biopsies fixed and stained using the new method, Preservation by Extraction and Fixation (PREF), and formalin fixed biopsies as controls. The results show that the morphology and cell architecture are well defined. Immunohistochemistry results for the PIN4 cocktail (basal keratin; p63; and racemase) were also satisfactory. The alcohol extracts were analyzed by metabolomics. With the high analytical sensitivity of mass spectrometry, hundreds of metabolites and candidate biomarkers were observed from individual prostate core needle biopsies. The metabolite profiles were collected and correlated with the histopathology results. CONCLUSIONS A novel method for performing small molecule biomarker analysis while retaining tissue architecture suitable for histopathology is presented. The combination of histopathology and metabolite biomarkers on the same biopsy specimen may lead to better clinical classifications of tumor aggressiveness. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e77 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dean Troyer Norfolk, VA More articles by this author Raymond Lance Norfolk, VA More articles by this author Klaus-Peter Adam Durham, NC More articles by this author Danny Alexander Durham, NC More articles by this author Jeffrey Shuster Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Got central prostate pathology review? A cross-sectional audit of 2009 versus 2003 outcomes.

196 Background: Prostate cancer is the most common non-cutaneous cancer in Canadian men; over 24,000 will be newly diagnosed and 4,300 will die from it in 2010. Estimating an individual's risk of disease spreading across the capsule and probability of recurrence with different treatment modalities is common practice in prostate cancer management and often drive the choice or extent of treatment options. A strong predictor of recurrence and organ confined disease is tumor grade. The literature recognizes differences in grading prostate cancer between genitourinary and non-specialized pathologists; we previously reported a 30% change in risk category (Low, GS 2-6; Int., GS 7; High, GS 8-10). However, this report was based on data from 2003/2004. A repeat audit was necessary given Gleason grading practice changes following the 2005 ISUP Consensus Conference. Methods: Log books from 2009/10 where our Genitourinary Pathologists (GUP) reviewed prostate needle core biopsies were used to identify cases; a retrospective chart review was completed. The following variables were extracted: 1° Gleason score; 2° Gleason score; number of sites; % Gleason 4/5 pattern (overall); perineural invasion (present/absent); extracapsular extension (present/absent). Descriptive statistics were used to summarize the results. Results: The charts of 132 patients having a GUP biopsy review were extracted. Seventeen percent (22/132) of cases changed risk category. Of the 47 low risk cases, 23% (11/47) were up-graded in risk category (21% by 1 category; 2% by 2 categories). Of the 46 intermediate risk cases, 15% (7/46) were up-graded and 2% (1/46) were down-graded. Of the 39 high risk cases, only 8% (3/39) were down-graded by 1 risk category. Comparatively, there was a 43% reduction in risk category change between 2003/04 (30%) and 2009/10 (17%). Conclusions: Despite this reduction, a clinically significant proportion of patients changed pathologic risk category upon GUP review. Thus, it is recommended that prostate cancer pathology be routinely reviewed by a GUP as a best practice to optimize management and quality of care. Strategies are still needed to address disparities in pathologic grading and represent a potential area for further investigation. No significant financial relationships to disclose.

Evaluation of metastatic potential of prostate cancer

We aimed to establish a method for evaluating malignant potential of prostate cancer using prostatic core needle biopsy (PCNB) before prostatectomy. If we can know the final pathological stage before treatment, we can select the most suitable therapeutic tactics. We then examined the expression of E-cadherin and type IV collagenase (MMP-9/-2), which play essential role in cancer cell invasion and metastasis. The expression ratio of MMP-9/-2 to E-cadherin (MER) is revealed as the relevant marker correlated with the final pathological stage and Gleason score by prostatectomy specimens. We next confirmed the significance of MER in PCNB, which means PCNB MER enables the prediction of the final pathologic stage at the cancer diagnosis. However, the methodology measuring MER is complicated to produce an observer-to-observer deviation. We then establish a bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. By this method, we can reduce an observer-to-observer deviation and a slide-to-slide deviation. The bicolor FISH-based MER is a useful tool for the preoperative evaluation of the final pathologic stage, by which we can assure a decision of prostatectomy indication.

Detection of TMPRSS2-ETS Fusions by a Multiprobe Fluorescence in Situ Hybridization Assay for the Early Diagnosis of Prostate Cancer : A Pilot Study

Fusion of the prostate-specific and androgen-regulated transmembrane-serine protease gene (TMPRSS2) with the erythroblast transformation-specific (ETS) family members is the most common genetic alteration in prostate cancer. However, the biological and clinical role of TMPRSS2-ETS fusions in prostate cancer, especially in problematic prostate needle core biopsies, has not been rigorously evaluated. We randomly collected 85 specimens including 50 archival prostate cancer tissue blocks, 15 normal prostate specimens, and 20 benign prostatic hyperplasia specimens for TMPRSS2-ETS fusion analyses. Moreover, the fusion status in an additional 20 patients with initial negative biopsies who progressed to biopsy-positive prostate cancer at subsequent follow-ups was also characterized. Fluorescently labeled probes specific for ERG-related rearrangements involving the TMPRSS2-ERG fusion as well as TMPRSS2-ETV1 and TMPRSS2-ETV4 were used to assess samples for gene rearrangements indicative of malignancy under a design of sequential trial. Rearrangements involving TMPRSS2-ETS fusions were detected in 90.0% of the 50 postoperative prostate cancer samples. The positive rate for the rearrangements in the initial prostate cancer-negative biopsies of 20 patients who eventually progressed to prostate cancer was 60.0% (12/20). Our preliminary study demonstrates that the clinical utility of TMPRSS2-ETS fusion detection as a biomarker and ancillary diagnostic tool for the early diagnosis of prostate cancer is promising, given this approach shows significant high sensitivity and specificity in detection.

Evaluation of routine application of P504S, 34βE12 and p63 immunostaining on 250 prostate needle biopsy specimens

We aimed to determine whether a standard P504S, 34betaE12 and p63 immunostaining of prostate core needle biopsy specimens can optimize diagnostic accuracy of conventional staining methods. The staining properties of all three antibodies were evaluated on 250 prostate biopsies formerly diagnosed as benign. Lack of basal cell staining in more than three glands for 34betaE12 and p63 occurred in 41 (27.5%) and 9 (6%) respective cases from the General Hospital pool. Respective figures from the Uropathology department specimens were 18 (18%) for 34betaE12 and 8 (8%) for p63. With the aid of P504S positivity, a case of prostate cancer as well as another of atypical small acinar proliferation was discovered. Despite its potential for important aid in accurate diagnosis, standard application of immunohistochemistry in prostate biopsy is not justified and should be reserved for equivocal cases where conventional pathology fails to be conclusive.

An improved method for constructing tissue microarrays from prostate needle biopsy specimens

Background:Prostate cancer diagnosis is routinely made by the histopathological examination of formalin fixed needle biopsy specimens. Frequently this is the only cancer tissue available from the patient for the analysis...