Atypical Small Acinar Proliferation Research Articles

IMMUNOHISTOCHEMICAL ANALYSIS AS A METHOD FOR INCREASING THE DETECTION OF PROSTATE CANCER IN PRIMARY BIOPSY

Morphological manifestations of prostate cancer (PCa) in 15–20% of cases are similar to those with benign hyperplastic processes in prostate tissue and/or with a histological pattern of atypical small acinar proliferation (ASAP). The purpose of this study is a comparative study of the detection of prostate cancer in biopsy material using a review morphological analysis and immunohistochemistry with the use of monoclonal antibodies to the nuclear p63 protein, high molecular weight cytokeratins of clone 34βE12 and α-methylacyl-CoA-racemase. Materials and methods . The method of the study was a retrospective analysis of the findings on the review morpholog­ical and immunohistochemical (IHC) analyzes of biopsy material of 428 patients who were examined and treated in the urological hospital for the period from 2013 to 2017. Results . Almost half of the cases of ASAP, determined by routine histological examination of biopsy specimens with hematoxylin-eosin staining, in the process of IHC analysis using monoclonal antibodies to the nuclear protein p63, cyto­keratins of clone 34βE12 and α-methylacyl-CoA racemase were verified for prostate cancer. The number of histological findings on benign prostatic hyperplasia detected in routinely stained preparations decreased by 12.38% in favor of the histological diagnosis of prostate cancer after the IHC study. Conclusion . Immunohistochemical analysis of biopsy material using monoclonal antibodies to nuclear p63, high-molec­ular cytokeratins of clone 34βE12 and α-methylacyl-CoA racemase for suspected prostate cancer: firstly, specifies the micromorphological picture and demasks prostate cancer; secondly, it increases the detectability of prostate cancer; thirdly, it reduces the occurrence of false-negative results.

MP18-06 CLINICOPATHOLOGIC IMPLICATIONS OF ATYPICAL SMALL ACINAR PROLIFERATION (ASAP) IN THE ERA OF ACTIVE SURVEILLANCE

INTRODUCTION AND OBJECTIVES:The diagnosis of atypical small acinar proliferation (ASAP) on prostatic needle biopsy (NB) is associated with a 30-40% cancer detection rate on subsequent NB. In the er...

Relationship between prostate cancer and atypical small acinar proliferation

Aim: To investigate the prostatic adenocarcinoma (PA) detection rate in follow up biopsies with an initial diagnosis of atypical small acinar proliferation (ASAP). Materials and Methods: In this study, the cases of ASAP diagnosis in prostate needle biopsy materials between January 2010 and December 2016 were retrospectively analyzed and the correlation between the results and the follow-up diagnoses of ASAP-diagnosed cases was investigated. Results: 62 cases with ASAP were included in the study and 21 (34%) of them were detected as PA after the follow-up diagnoses. Also ASAP and PA were detected at different localizations in 38% of the cases. Conclusion: We are on the opinion that it is important to increase the number of samples taken from other localizations as well as ASAP diagnosed quadrants when taking follow-up biopsies.

Mean Platelet Volume as an Inflammation Marker, Possible Biomarker of Tumor Detection in Prostate Biopsy

Background: In the diagnosis of prostatic diseases, the need for markers other than prostate specific antigen (PSA) has been increasing in recent years. So, we aimed to determine the predictive value, the neutrophil lymphocyte ratio, platelet-to-lymphocyte ratio and mean platelet volume before prostate biopsy in predicting the results of pathology. Transrectal ultrasound-guided biopsy of the prostate was performed because of high PSA values and compared values of these parameters to predict of pathology results. Methods: 2715 patients who underwent 10 - 12 quadrant transrectal ultrasound-guided prostate biopsies between January 2008 and January 2018 have been evaluated retrospectively. Patients were divided into groups according to the biopsy pathology results by benign (group 1), atypical small acinar proliferation (ASAP) (group 2) and prostate cancer (group 3). A total of 204 patients who were benign prostate hyperplasia in 71 patients (34.8%), atypical small acinar proliferation in 80 (39.21%) and prostate adenocarcinoma (PCa) in 53 patients (25.98%) were included in the study by systematic sampling. Before the biopsy total PSA (tPSA), free PSA (fPSA), rate of percentage of free to total prostate specific antigen (f/tPSA) rate, PSA density (PSA-D), white blood cell (WBC) count, blood neutrophil count (NC), blood lymphocyte count (LC), neutrophil lymphocyte ratio (NLR), mean platelet volume (MPV), platelet count (PLT) and platelet-to-lymphocyte ratio (PLR) were measured and compared in all groups. Differences in continuous variables were assessed using the ANOVA. Logistic regression was used to analyze the linear relationship between predictive variables and pathology results. P Results: NLR and PLR values were lower in group 1 than group 2 and were found statistically significant between in group 1 and group 2 (p: 0.03 and p: 0.02, respectively). MPV value was found 1.7 times higher in patients who were diagnosed with ASAP pathology than those with benign pathologies. Although there was statistically significant increase in MPV values in logistic regression results, no statistically significant diagnostic value was found. In addition MPV value was found 0.5 times higher in patients who were diagnosed patients with ASAP than prostate cancer group. ROC analysis showed that the optimal threshold was 7.65 femtoliter (sensitivity: 51%; specificity: 30%) and was found to be a statistically significant diagnostic value to distinguish groups 2 and 3. The lowest value of MPV was found in group 3. Conclusions: In cases where the PSA value is insufficient in predicting the pathology result, the effect of NLR, PLR and MPV on differential diagnosis can be kept in mind. While NLR and PLR are more useful in the diagnosis of ASAP, MPV is more effective in the diagnosis of malignancy.

Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy.

PurposeWe evaluated factors predicting a positive repeat biopsy result in patients with an initial negative prostate biopsy result.Materials and MethodsThis study included 124 patients in whom prostate cancer (PCa) was not detected in the initial transrectal ultrasound-guided prostate biopsy and who underwent repeat biopsy from January 2011 to December 2017. Patients without PCa in both initial and repeat prostate biopsies were designated as group 1 (n=82), and those in whom PCa was detected on a repeat prostate biopsy were designated as group 2 (n=42). Among group 2 patients, 6 had insignificant PCa according to the Epstein criteria and were combined with group 1 patients to make up group A (n=88). Patients with significant PCa were categorized as group B (n=36). We compared clinicopathologic characteristics between the groups.ResultsMultivariate analysis showed that age (p=0.018) and detection of atypical small acinar proliferation (ASAP) or ≥3 cores of high-grade prostatic intraepithelial neoplasia (HGPIN) (p=0.011) on the initial biopsy were predictive factors for a positive result on a repeat biopsy. When we compared group A and group B, age (p=0.004) and the De Ritis ratio (p=0.024) were significantly higher in group B in the multivariate analysis.ConclusionsAge and the detection of ASAP or ≥3 cores of HGPIN on the initial biopsy were associated with detection of PCa on a repeat biopsy. Age and the De Ritis ratio were found to be predictive factors for the detection of clinically significant PCa on a repeat biopsy.

Role of apparent diffusion coefficient values in prostate diseases characterization on diffusion-weighted magnetic resonance imaging.

To evaluate if normal and pathological prostate tissue can be distinguished by using apparent diffusion coefficient (ADC) values on magnetic resonance imaging (MRI) and to understand if it is possible to differentiate among pathological prostate tissues using ADC values. Our population consisted in 81 patients (mean age 65.4 years) in which 84 suspicious areas were identified. Regions of interest were placed over suspicious areas, detected on MRI, and over areas with normal appearance, and ADC values were recorded. Statistical differences between ADC values of suspicious and normal areas were evaluated. Histopathological diagnosis, obtained from targeted biopsy using MRI-US fusion biopsies in 39 patients and from prostatectomy in 42 patients, were correlated to ADC values. Histopathological diagnosis revealed 58 cases of prostate cancer (PCa), 19 patients with indolent PCa (Gleason Score ≤6) and 39 patients with clinically significant PCa (Gleason Score ≥7), 16 of high-grade prostatic intraepithelial neoplasia (HG-PIN) and 10 of atypical small acinar proliferation (ASAP). Significant statistical differences between mean ADC values of normal prostate tissue versus PCa (P<0.00001), HG-PIN (P<0.00001) and ASAP (P<0.00001) were found. Significant differences were observed between mean ADC values of PCa versus HG-PIN (P<0.00001) and ASAP (P<0.00001) with many overlapping values. Differences between mean ADC values of HG-PIN versus ASAP (P=0.015) were not significant. Significant differences of ADC values were also observed between patients with indolent and clinically significant PCa (P<0.00001). ADC values allow differentiation between normal and pathological prostate tissue and between indolent and clinically significant PCa but do not allow a definite differentiation between PCa, HG-PIN, and ASAP.

P070 - The potentials of AR, AR-regulated TMPRSS2-ERG fusion and KLK3 mRNAs for prostate cancer risk assessment in suspicious prostate biopsy cores with atypical small acinar proliferation

P070 - The potentials of AR, AR-regulated TMPRSS2-ERG fusion and KLK3 mRNAs for prostate cancer risk assessment in suspicious prostate biopsy cores with atypical small acinar proliferation

RNA-based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP-2 upregulation for a subsequent prostate cancer diagnosis.

Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC-related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9. PC-related RNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) system in pathologically ASAP-diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4-10 ng/mL. We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP-2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP-2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow-up period (P = 0.003). Although, more clinical validations are needed for the stratification of PC risk in ASAP-diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP-2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP-diagnosed patients with a PSA level of 4-10 ng/mL.

Initial diagnosis of insignificant cancer, high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, and negative have the same rate of upgrade to a Gleason score of 7 or higher on repeat prostate biopsy

Extended prostate needle core biopsies are standard of care for the diagnosis of prostatic carcinoma. Subsequent biopsies may be performed for a variety of indications. Knowledge of biopsy characteristics indicating risk for progression may have utility to guide therapeutic management. Prostate needle core biopsies performed between 2008 and 2014 were reviewed. Patients with at least 1 subsequent biopsy were identified. Cases were categorized by worst initial diagnosis. Gleason ≤6 carcinoma was further classified as significant or insignificant with insignificant defined as follows: ≤2 cores with carcinoma, sites with ≤50% carcinoma, and unilateral carcinoma. A total of 329 men underwent repeat biopsies. Gleason ≤6 insignificant carcinoma, high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation, and negative biopsies had a similar rate of Gleason ≥7 upon repeat biopsy (16%, 17%, 14%; P = .91). Initial biopsy diagnoses of Gleason ≤6 significant carcinoma had a higher rate of Gleason ≥7 on repeat biopsy compared with initial biopsies of Gleason ≤6 insignificant carcinoma (39%, 16%; P = .003). Within initial diagnoses of Gleason ≤6, 1 core compared with more than 1 core positive had a lower rate of Gleason ≥7 on repeat biopsy (17%, 30%), although this difference was not significant (P = .08). An initial biopsy diagnosed as Gleason ≤6 insignificant carcinoma, HGPIN and/or atypical small acinar proliferation, or negative had a similar substantial risk of Gleason ≥7 carcinoma upon subsequent biopsy. Our findings support the continued stratification of Gleason ≤6 and thus the diagnostic workup of all atypical foci to provide an accurate, thorough number of involved cores.

MP40-05 EFFECTS OF INTRODUCING PRE-BIOPSY MPMRI INTO CONTEMPORARY UK PROSTATE CANCER DETECTION.

You have accessJournal of UrologyProstate Cancer: Detection & Screening III1 Apr 2018MP40-05 EFFECTS OF INTRODUCING PRE-BIOPSY MPMRI INTO CONTEMPORARY UK PROSTATE CANCER DETECTION. Catherine Hobbs, Katie Eyre, Robert McCormick, Fergus Gleeson, Ruth MacPherson, Clare Verrill, Freddie Hamdy, Simon Brewster, and Richard Bryant Catherine HobbsCatherine Hobbs More articles by this author , Katie EyreKatie Eyre More articles by this author , Robert McCormickRobert McCormick More articles by this author , Fergus GleesonFergus Gleeson More articles by this author , Ruth MacPhersonRuth MacPherson More articles by this author , Clare VerrillClare Verrill More articles by this author , Freddie HamdyFreddie Hamdy More articles by this author , Simon BrewsterSimon Brewster More articles by this author , and Richard BryantRichard Bryant More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1272AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pre-biopsy multiparametric magnetic resonance imaging (PB-mpMRI) using the Prostate Imaging Reporting and Data System (PI-RADS) has become an adjunct to prostate cancer (PCa) diagnosis, and was incorporated into our PCa diagnostic pathway in July 2016. Interrogating our PCa series, we hypothesized that PB-mpMRI increases the diagnostic yield of transrectal prostate biopsy (TRPB), and may allow us to discontinue recommending systematic TRPB to men with a ″negative″ MRI. METHODS 997 patients underwent TRPB without PB-mpMRI in 18 months to June 2016 (cohort A), and 792 patients underwent TRPB following PB-mpMRI during the 12 months from July 2016 (cohort B), all patients being previously biopsy-naive. Patients with PB-mpMRI lesions (PI-RADS 3-5) underwent cognitive targeted plus systematic TRPB, whilst patients without targetable lesions underwent systematic TRPB. We investigated the impact of introducing PB-mpMRI on the diagnostic yield of TRPB. RESULTS Cohort B comprised younger (median 68 v 69 years, p=0.001) men with a lower PSA (median 7.6 v 7.9 ng/mL, p=0.032) and prostate volume (median 56.7 v 62 cc, p=0.006) compared with cohort A. No difference was seen in family history, finasteride use, or PSA-density (p>0.05 for each). We observed increased detection of multi-focal prostatic intraepithelial neoplasia ± atypical small acinar proliferation (p=0.018) and increased maximum PCa core length (≥5mm versus <5mm, p=0.041) in Cohort B, but no difference in overall PCa detection (57.6 v 56.7%), Gleason Grade (GG), or number of positive cores (p>0.05 for each), compared with cohort A. We also observed a significant shift towards PCa radical intervention (surgery and/or radiotherapy) for Cohort B (p<0.001). A significant correlation was observed between the PI-RADS score and overall biopsy result (R=0.612, p<0.001) and GG (R=0.569, p<0.001). 49.9% of PB-mpMRIs revealed PI-RADS 4/5 lesions (% Sensitivity, Specificity, PPV and NPV for GG Group 2-5 PCa 79.6, 78.5, 78.1 and 80.1 respectively for PI-RADs 4/5 lesions). The % sensitivity, specificity, PPV and NPV of combined PI-RADs 1/2 lesions for GG Group 2-5 PCa was 88.1, 59.8, 67.8 and 84 respectively. CONCLUSIONS 1) Introducing PB-mpMRI into our contemporary PCa detection pathway increased the diagnostic yield of TRPB by increasing the maximum cancer length per biopsy core. This may explain the observed shift towards more radical treatment interventions for PCa.2) A ″negative″ MRI scan (PI-RADS 1/2) missed GG group 2 or higher PCa detected by systematic TRPB in 16% of cases (i.e. approximately 1 in 6 cases), highlighting the need to recommend both investigations for men referred with suspected PCa. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e521 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Catherine Hobbs More articles by this author Katie Eyre More articles by this author Robert McCormick More articles by this author Fergus Gleeson More articles by this author Ruth MacPherson More articles by this author Clare Verrill More articles by this author Freddie Hamdy More articles by this author Simon Brewster More articles by this author Richard Bryant More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP17-14 THE PROGNOSTIC IMPACT OF A NEGATIVE CONFIRMATORY BIOPSY IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II1 Apr 2018MP17-14 THE PROGNOSTIC IMPACT OF A NEGATIVE CONFIRMATORY BIOPSY IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Keyan Salari, Dimitar Zlatev, David Kuppermann, Mark Preston, Douglas Dahl, Jason Efstathiou, Michael Blute, Anthony Zietman, and Adam Feldman Keyan SalariKeyan Salari More articles by this author , Dimitar ZlatevDimitar Zlatev More articles by this author , David KuppermannDavid Kuppermann More articles by this author , Mark PrestonMark Preston More articles by this author , Douglas DahlDouglas Dahl More articles by this author , Jason EfstathiouJason Efstathiou More articles by this author , Michael BluteMichael Blute More articles by this author , Anthony ZietmanAnthony Zietman More articles by this author , and Adam FeldmanAdam Feldman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.569AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Active surveillance (AS) is increasingly used in managing low-risk and favorable intermediate-risk prostate cancer. To mitigate the risk of unsampled higher risk disease, most institutional AS protocols call for a confirmatory prostate biopsy within 12-18 months following initial diagnostic biopsy. Here, we investigate whether the results of confirmatory biopsy impact the outcomes of men on AS. METHODS We retrospectively reviewed our institutional database of men enrolled in AS between 1997-2014 with a minimum follow-up of 6 months (n = 974). Biopsies with any prostate cancer were considered positive. Biopsies containing only benign prostatic tissue, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation (ASAP) were considered negative. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS At diagnosis, median age was 67 years (IQR 62-72) and median PSA was 5.1 ng/mL (IQR 3.9-6.8). The vast majority of patients had Gleason ≤6 (97%) and clinical stage T1 (92%) disease. With a median follow-up of 4.8 years, 702 (72%) patients underwent a confirmatory biopsy. 67% of confirmatory biopsies were positive for prostate cancer; 33% were negative (167 benign, 40 PIN, and 22 ASAP). Of the 702 patients, 33% progressed to treatment, with pathologic progression the most common reason (77%). Univariate predictors of progression to treatment included initial clinical stage (P=0.04), involvement of >20% of any core on diagnostic biopsy (P <0.01), PSA density ≥0.15 (P <0.001), and confirmatory biopsy status (P <10-14). In multivariate analysis, a negative confirmatory biopsy remained the strongest predictor of progression to treatment (HR 0.12 [95%CI 0.06-0.24], P < 10-8). Confirmatory biopsy status was not associated with risk of adverse pathology on RP, metastasis-free survival, disease-specific survival, or overall survival. CONCLUSIONS A negative confirmatory biopsy is associated with a significantly lower rate of progression to treatment among men on AS. This may serve as a useful tool for prognostication and help determine the need for further repeat biopsies for men on AS. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e210 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Keyan Salari More articles by this author Dimitar Zlatev More articles by this author David Kuppermann More articles by this author Mark Preston More articles by this author Douglas Dahl More articles by this author Jason Efstathiou More articles by this author Michael Blute More articles by this author Anthony Zietman More articles by this author Adam Feldman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The prognostic impact of a negative confirmatory biopsy in men on active surveillance for prostate cancer.

76 Background: Active surveillance (AS) is increasingly used in managing low-risk and favorable intermediate-risk prostate cancer. To mitigate the risk of unsampled higher risk disease, most institutional AS protocols call for a confirmatory prostate biopsy within 12-18 months following initial diagnostic biopsy. Here, we investigate whether the results of confirmatory biopsy impact the outcomes of men on AS. Methods: We retrospectively reviewed our institutional database of men enrolled in AS between 1997-2014 with a minimum follow-up of 6 months (n = 974). Biopsies with any prostate cancer were considered positive. Biopsies containing only benign prostatic tissue, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation (ASAP) were considered negative. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: At diagnosis, median age was 67 years (IQR 62-72) and median PSA was 5.1 ng/mL (IQR 3.9-6.8). The vast majority of patients had Gleason ≤6 (97%) and clinical stage T1 (92%) disease. With a median follow-up of 4.8 years, 702 (72%) patients underwent a confirmatory biopsy. 67% of confirmatory biopsies were positive for prostate cancer; 33% were negative (167 benign, 40 PIN, and 22 ASAP). Of the 702 patients, 33% progressed to treatment, with pathologic progression the most common reason (77%). Univariate predictors of progression to treatment included initial clinical stage ( P= 0.04), involvement of &gt; 20% of any core on diagnostic biopsy ( P &lt; 0.01), PSA density ≥0.15 ( P &lt; 0.001), and confirmatory biopsy status ( P &lt; 10-14). In multivariate analysis, a negative confirmatory biopsy remained the strongest predictor of progression to treatment (HR 0.12 [95%CI 0.06-0.24], P &lt; 10-8). Confirmatory biopsy status was not associated with risk of adverse pathology on RP, metastasis-free survival, disease-specific survival, or overall survival. Conclusions: A negative confirmatory biopsy is associated with a significantly lower rate of progression to treatment among men on AS. This may serve as a useful tool for prognostication and help determine the need for further repeat biopsies for men on AS.

Which factors allow to anticipate the diagnosis of prostate cancer in pin patients? a study on 546 patients

To analyze which factors allow to assess the risk of finding a prostate cancer (PCa) at repeated biopsies in patients with diagnosis of prostatic intraepithelial neoplasia (PIN). At our institute all patients with a diagnosis of PIN undergo a 6-monthly control biopsy until the achievement of a benign histology or up to a maximum of 4 consecutive biopsies. For this study a retrospective review of clinical and bioptic data of patients with a diagnosis of isolated PIN (i.e. without associated atypical small acinar proliferation or small cancer foci) was carried out. The correlation between these features and the probability to find PCa at the first re-biopsy or at a further re-biopsy was independently analyzed. The data of 546 patients subjected to a median number of 3 biopsies, (mean: 10.8 and 12.9 cores at initial biopsy and at first re-biopsy, respectively), and with a mean “bioptic” follow-up time of 14.8 months, were analyzed. PCa was found in 174 cases (31.8%): for 116 of them it took place at the first re-biopsy, with a mean latency of 7.8 months from PIN diagnosis, whereas for 58 at a further re-biopsy, with a mean latency of 21.6 months. The risk of diagnosing PCa at the first re-biopsy was statistically correlated with the PSA value--for which a cut-off value of 7 ng/mL was identified--and with an anomalous rectal prostatic examination at the time of the initial biopsy. Differently, the risk of diagnosing PCa after the first re-biopsy correlated with the number of cores positive for PIN at the initial biopsy--for which a cut-off of 4 was identified--and to the ratio between these and the total number of cores, defined as PIN density--for which a cut-off of 50% was determined. DISCUSSION AND CONCLUSIONS. It is possible to suggest a tailored protocol of controls in patients with a diagnosis of PIN on the basis of the data available at the initial biopsy: a) high PSA value and/or an anomalous prostatic rectal examination: the diagnosis of PCa is probably just unacknowledged by the initial sampling and it is advisable to carry out an early re-biopsy; b) number of cores with PIN equal to or higher than 4 and/or PIN density equal to or higher than 50%: a true transition from PIN to PCa is likely to happen with time and it is advisable to carry out a delayed re-biopsy; c) no risk factors: just clinical and PSA monitoring to establish the indication to re-biopsy.

Outcomes of Prostate Atypical Small Acinar Proliferation and High-Grade Prostate Intraepithelial Neoplasm Patients

Objective: Atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two pathological findings occasionally noted in prostate biopsies. Previous Western studies reported that they were associated with prostate cancer. However, none Taiwanese series report the subsequent cancer detection in ASAP and HGPIN patients. This study aimed to examine the results of repeated biopsies in the patients with ASAP and HGPIN. Materials and Methods: A total of 220 consecutive patients with ASAP and/or HGPIN at our institute between January 1990 and December 2010 were enrolled. Patient demographics and clinical information were extracted from the electronic database of our institute. Prostate biopsies were performed through transrectal ultrasound guidance. The patients who had concurrent prostate cancer (n = 51) and no repeated prostate biopsies (n = 103) were excluded from the study. Patients with biopsy pathologies reporting low-grade prostatic intraepithelial neoplasia (n = 2) were also excluded. The remaining 64 patients were available for the final analysis. Results: Nearly, 38, 24, and 2 patients were initially diagnosed as ASAP, HGPIN, and ASAP along with HGPIN, respectively. After 10 years of follow-up, 36.8% patients in ASAP group developed prostate cancer, while 16.7% in HGPIN group and 100% in ASAP + HGPIN group. Median time to developing prostate cancer were 20 months in ASAP group, 31 months in HGPIN group, and 48 months in ASAP + HGPIN group. There was no significant difference of prostate cancer development between ASAP and HGPIN group (P = 0.291). Only older age, classified by 65 years, was significantly associated with a higher detection rate of prostate cancer. Conclusion: Patients with the initial diagnosis of ASAP or PIN has a high risk of developing prostate cancer. Therefore, those patients should be well announced and followed regularly.

Predictive value of neutrophil-to-lymphocyte ratio before the second biopsy while detecting atypical small acinar proliferation

Aim: In this study, we aimed to detect of predictive valueof neutrophil-to-lymphocyte ratio before the second biopsy while detecting atypical small acinar proliferation (ASAP) in high prostate-specific antigen (PSA) level.Material and Methods: Two thousand two hundred ninety five patients underwent 10-12 quadrant TRUSBP between January 2008 and January 2016 have been evaluated retrospectively. Seventy sixpatients, whose data were reached, are taken into the study. Before the first biopsy,total PSA (tPSA), free PSA (fPSA), rate of percentage of free to total prostate specific antigen (f/tPSA) rate, PSA density (PSAD),blood neutrophil count (NC) and neutrophil-to-lymphocyte ratio (NLR)were measured. Second biopsy results and changes in the data are compared.Results: Benign prostate hyperplasia in 44 patients (57.89%),ASAP in 16 (21.05%) and prostate adenocarcinoma (PCa) in 16 patients (21.05%)was detected. The patient’s age, tPSA, fPSA, t/fPSA, PSAD,NC and NLR were 63.29 years, 8.68ng/mL, 1.87ng/mL, 21.34%, 18.15 ng/ml2, 5.2710^3/μL and 2.95 in group 1 and 64.31 years, 8.62 ng/mL, 1.58ng/mL,21.01%, 20.18 ng/ml2, 7.5310^3/μL and 2.84 in group 2, respectively. Patient’s age, tPSA, fPSA, f/tPSA, PSAD, NC and NLR were not statistically significant between in two groups (p >0,05).Conclusions: We think that inflammation is a stimulant factor for PCa in patients with ASAP. So, before the first biopsy, it may be able to predict a cancer by considering NC and NLR in patients with ASAP. Although not significant, NC and NLR values were found to be higher in ASAP/malign than benign cases in the evaluation of ASAP patients before the second biopsy.Keywords: Prostate Cancer; Atypical Small Acinar Proliferation; Neutrophil-To-Iymphocyte Ratio.

Transrectal ultrasound-guided prostate rebiopsy: How many core sampling should be applied to which patient?

Background:We investigated the correlation between the sampled number of cores in rebiopsy and the cancer detection rate (CDR).Materials and Methods:Two hundred and twelve patients with normal rectal examination who had undergone rebiopsy in the past 5 years were examined retrospectively. Moreover, 68% of them had undergone 12 cores (Group 1) while 32% had undergone 20 cores (Group 2). Both groups were compared with respect to the CDR.Results:There was no difference between groups in terms of age, total prostate-specific antigen, and prostate volume (P > 0.05). Forty-one (19%) of 212 patients were diagnosed with cancer, and the CDR was significantly higher in Group 2 (30.9% vs. 13.9%, P = 0.004). This rate increased from 6.5% to 20% (P = 0.025) and from 0% to 33.3% (P = 0.023), respectively, with 12-core and 20-core rebiopsies in patients whose initial pathology indicated benign and high-grade prostatic intraepithelial neoplasia (HGPIN). Furthermore, cancer was detected in 24 (40%) of 60 patients who were diagnosed with atypical small acinar proliferation (ASAP) in the initial biopsy. However, despite being higher in 20-core biopsy group (47.6% vs. 35.9%), this was not statistically significant (P = 0.377).Conclusions:At least 20 cores should be sampled in rebiopsy, especially in the patients diagnosed with benign and HGPIN. However, we believe that standard systematic sampling will be sufficient for the patients diagnosed with ASAP.

T2E (TMPRSS2-ERG) fusion transcripts are associated with higher levels of AMACR mRNA and a subsequent prostate cancer diagnosis in patients with atypical small acinar proliferation

Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 (TMPRSS2) and genes from the ETS transcription factor family, most commonly ERG and ETV1, result in alteration that responsible for oncogenic activity in prostate cancer (PC). The aims of the present study were to: 1) investigate the frequency of these fusion transcripts in prostate tissue samples obtained from patients diagnosed with atypical small acinar proliferation (ASAP), 2) determine any clinical significance of T2E expression at the RNA level in predicting PC detection in subsequent biopsies, and 3) evaluate expression of the PC marker, alpha-methylacyl-CoA racemase (AMACR), according to T2E status by real-time quantitative reverse transcription PCR (RT-qPCR). T2E transcripts were detected in 31.7% (n=20) of the patients examined, and this was significantly associated with subsequent detection of PC in ASAP patients with a prostate specific antigen (PSA) level of 4–10ng/ml (p=0.045). AMACR expression was also significantly higher in the patients who were diagnosed with PC in subsequent biopsies than in the patients who were not diagnosed with PC (p=0.034) and in T2E-positive ASAP patients (p=0.002) compared to T2E-negative ASAP patients. Although these results need to be further clinically validated, we suggest that the presence of T2E transcript, in association with higher AMACR expression, is an indicator of PC risk from a T2E-positive focus or an unsampled malignant gland adjacent to a T2E-positive site in ASAP lesions.

Impact of the Pathologist on Prostate Biopsy Diagnosis and Immunohistochemical Stain Usage Within a Single Institution.

To determine whether pathologists in a tertiary care institution vary in diagnosis and immunohistochemical stain usage in prostate biopsy specimens. Men who underwent prostate needle biopsies between 2008 and 2013 were included. In total, 1,777 prostate biopsy specimens diagnosed by nine pathologists showed variation in diagnostic reporting (atypical small acinar proliferation, 2.0%-8.0%; high-grade prostatic intraepithelial neoplasia, 2.0%-8.5%; nonneoplastic, 30.2%-48.3%; adenocarcinoma, 46.2%-55.3%; P < .001). Variation in Gleason scoring was observed (P < .001), with the 4 + 3 = 7 category having the greatest variability (6.9%-30.3%). A blinded review from the most outlying pathologist in this category revealed 45% grading discrepancies. The mean number of immunostains performed per case (0.3-1.2) differed between pathologists (P < .001), and one pathologist used immunostains at twice the rate of the remaining cohort. Case pathologist significantly affects prostate biopsy diagnosis and immunohistochemical workup. We recommend evaluation for outlying practice patterns to provide consistent and efficient patient care.

Clinical Significance of Measuring Global Hydroxymethylation of White Blood Cell DNA in Prostate Cancer: Comparison to PSA in a Pilot Exploratory Study

This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP. We observed a wider heterogeneity in 5hmC content in all of the prostate pathologies analyzed when compared to the healthy age-matched controls. When compared to blood levels of prostate-specific antigen (PSA), this 5hmC-based biomarker had a lower performance in PCa detection than the use of a PSA cut-off of 2.5 nanograms per milliliter (ng/mL). Above this threshold, however, it delineated almost three quarters of PCa patients from controls and patients with other prostate pathologies. Overall, genome-wide 5hmC content of WBC DNA appears to be applicable for detecting non-cancerous prostate diseases, rather than PCa. Our results also suggest a potential clinical usefulness of complementing PSA as a PCa marker by the addition of a set of hydroxymethylation markers in the blood, but further studies are necessary to confirm these findings.

Atypical small acinar proliferation at index prostate biopsy: rethinking the re-biopsy paradigm.

Guidelines for atypical small acinar proliferation (ASAP) diagnosed on prostate biopsy recommend repeat biopsy within 3-6months after diagnosis. We sought to discern the rate of detecting clinically significant prostate cancer on repeat biopsy and predictors associated with progression. We performed a retrospective chart review of patients who underwent prostate biopsy at our institution from January 1, 2008, to December 31, 2015. Gleason grade group (GGG) system and D'Amico stratification were used to report pathology and risk stratification, respectively. Logistic and linear regression analyses were performed. A total of 593 patients underwent transrectal ultrasound-guided prostate biopsy, of which 27 (4.6%) had the diagnosis of ASAP. Of these, 11 (41%) had a repeat biopsy. Median time from diagnosis to repeat biopsy was 147days (IQR 83.5-247.0). Distribution across the GGG system on repeat biopsy was as follows: 7 (63.6%) benign, 3 (27.3%) GG1, and 1 (9.1%) GG2. ASAP was not associated with subsequent diagnosis of clinically significant prostate cancer (OR 0.46, 95% CI 0.064-3.247, P=0.432). There was no association between ASAP and high cancer risk (ASAP: β=-0.12; P=0.204). Patients diagnosed with ASAP managed according to guideline recommendations are more likely diagnosed with benign pathology and indolent prostate cancer on repeat biopsy. These findings support prior studies suggesting refinement of guidelines in regard to the appropriateness and timeliness of repeat biopsy among patients diagnosed with ASAP.