The importance of histomorphological features and ERG expression in the diagnosis of malignancy in cases with atypical small acinar proliferation.

BACKGROUND: Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy. METHODS: Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically. RESULTS: Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002). CONCLUSIONS: Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

Can MRI Help Inform Which Men With a History of Multifocal High-Grade Prostatic Intraepithelial Neoplasia or Atypical Small Acinar Proliferation Remain at an Elevated Risk for Clinically Significant Prostate Cancer?

PURPOSE: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy. MATERIALS AND METHODS: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy. Men with an MRI prior to the index biopsy were excluded. We compared the proportion of men with ≥ GG2 CaP (Grade Group 2 prostate cancer) on repeat biopsy among the following groups with the χ2 test: no MRI, PIRADS (Prostate Imaging-Reporting and Data System) ≥ 4, and PIRADS ≤ 3. Multivariable models were used to estimate the adjusted association between MRI findings and ≥ GG2 CaP on repeat biopsy. RESULTS: Among the 207 men with a previous diagnosis of ASAP/multifocal HGPIN that underwent a repeat biopsy, men with a PIRADS ≥ 4 lesion had a higher proportion of ≥ GG2 CaP (56%) compared with men without an MRI (12%, P < .001). A lower proportion of men with PIRADS ≤ 3 lesions had ≥ GG2 CaP (3.0%) compared with men without an MRI (12%, P = .13). In the adjusted model, men with a PIRADS 4 to 5 lesion had higher odds (OR: 11.4, P < .001) of ≥ GG2 CaP on repeat biopsy. CONCLUSIONS: MRI is a valuable diagnostic tool to triage which men with a history of ASAP or multifocal HGPIN on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP.

Expression of nectin-4 in prostate cancer.

OBJECTIVE: Nectin-4 is a transmembrane protein belonging to the nectin family of immunoglobulin-like molecules which is found in the placenta and trachea under physiological conditions and its expression has been shown in many cancer types. We aimed to investigate for the 1st time nectin-4 expression in human prostate cancer tissues. METHODS: We retrospectively analyzed the prostate pathology specimens of 82 patients who underwent initial transrectal ultrasound-guided prostate biopsy or transurethral prostate resection and were found to have atypical small acinar proliferation (ASAP) and incidentally prostate cancer. Tissue samples with prostatic cancer were used as a control for alpha-methylacyl-CoA racemase (AMACR), and benign prostatic glands in the same tissue provided the negative control. The intensity and extent of nectin-4 expression were determined microscopically using the histochemical scoring system which was defined as the product of the staining intensity (score: 0-3) and percentage of stained cells (0-100) at a given intensity. RESULTS: We conducted immunohistochemical analysis of nectin-4 and AMACR expression in all 82 samples. While AMACR expression was positive in prostate cancer tissues with a GS of <7 (n=24, 100%), 7 (n=18, 100%), and ≥8 (n=15, 100%), it was negative in all ASAP samples (n=25, 100%) (p<0.001). Nectin-4 expression was not detected in any of the GS <7, GS 7, or GS ≥8 samples but was found in benign prostatic gland tissues and all 25 (100%) ASAP samples (p<0.001). CONCLUSION: We found that nectin-4 was not expressed in prostate cancer tissues but was expressed in ASAP-and benign prostate gland containing tissues. We believe that prospective studies with more patients and samples including radical prostatectomy materials will reveal the relationship between nectin-4 and prostate cancer more clearly.

[A single center study：An analysis of the safety and validity of delaying repeated biopsy for patients with atypical small acinar proliferation].

OBJECTIVE: To explore the association between atypical small acinar proliferation (ASAP) and subsequent diagnosis of intermediate and high risk prostate cancer (PCa), and analyze whether delaying repeat biopsy timing is safe and effective. METHODS: From June 2000 to June 2022, we retrospectively analyzed the clinical data of 276 patients accepting prostatic biopsy and diagnosed with ASAP in China-Japan Union Hospital of Jilin University. 54.7% (151/276) patients had a repeat biopsy. We used statistic methods to process the data. RESULTS: 25.2%（38/151）patients were diagnosed with PCa on repeat biopsy. Among them, 78.9%（30/38）patients had Gleason score (GS) 3+3 and 21.1% (8/38) had GS 3+4 disease. There were 4 and 6 patients got RP respectively in the two cohorts. Only 5.3% (8/151) of ASAP patients were diagnosed as intermediate risk PCa in repeated biopsy and specially, no high risk PCa was identified in our study. CONCLUSION: It was safe and valid to delay the repeat biopsy.

[Significance of atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia in prostate biopsy in China].

OBJECTIVE: To assess the rates of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) detected in prostate biopsy in China and the risk of PCa found in subsequent repeat biopsy. METHODS: A total of 2,456 patients underwent TRUS-guided prostate biopsy with the samples of ASAP and/or HGPIN tissues in our hospital at least twice between July 2014 and June 2019. We analyzed the findings of digital rectal examination, prostate volumes, PSA levels, and the results of prostate biopsies. RESULTS: Initial prostate biopsies revealed 737 cases of PCa (30.0%), 215 cases of ASAP (8.8%), 98 cases of HGPIN (4.0%), and 18 cases of ASAP+HGPIN (0.7%). Totally, 313 of the patients met the inclusion criteria and included in this study. Of the 215 cases of ASAP confirmed in the first biopsy, 72 and 25 were diagnosed with PCa in the second and third biopsies, respectively, 83 with Gleason score (GS) 6, 14 with GS7, 57 with T1c and 40 with T2a tumors. Of the 98 cases of HGPIN confirmed in the first biopsy, 1 was diagnosed with PCa in the second and another 1 in the third biopsy, both with GS6 and T1c tumors. Of the 18 cases of ASAP+HGPIN confirmed in the first biopsy, 7 and 3 were diagnosed with PCa in the second and third biopsies, respectively, 7 with GS6, 3 with GS7, 6 with T1c and 4 with T2a tumors. CONCLUSIONS: ASAP is a significant risk factor for PCa and repeat prostate biopsy should be performed for patients diagnosed with ASAP in the first biopsy. Whether repeat biopsy is necessary for those diagnosed with HGPIN depends on other related clinical parameters./.

Valor actual de los hallazgos histológicos de biopsias de próstata negativas en la predicción del riesgo futuro de cáncer de próstata clínicamente significativo / The current value of histological findings in negative prostate biopsies to predict the future risk of clinically significant prostate cancer

Introducción: Se recomienda realizar una biopsia prostática (PBx) de repetición ante una sospecha persistente de cáncer de próstata (PCa) o cuando se identifica proliferación acinar atípica (ASAP), neoplasia intraepitelial de alto grado (HGPIN) extensa (≥3 zonas de biopsia) o HGPIN con células atípicas sospechosas de adenocarcinoma (PIN-ATYP). Actualmente se recomienda realizar una resonancia magnética multiparamétrica (mpMRI) y PBx guiada por mpMRI (MRI-TBx) en una PBx de repetición. Nuestro objetivo fue analizar el valor actual para predecir el riesgo de PCa clínicamente significativo (csPCa) del hallazgo de ASAP, mHGPIN, PIN-ATYP y otros hallazgos histológicos.MétodosSe realizó un análisis retrospectivo de 377 PBx de repetición. Se realizó MRI-TBx cuando la puntuación PI-RADS fue≥3 y PBX sistemáticas de 12 cilindros guiadas por ecografía transrectal (TRUS) cuando fue≤2. ASAP, HGPIN, HGPIN multifocal (mHGPIN), PIN-ATYP y otros 8 hallazgos histológicos fueron reportados prospectivamente en las PBx negativas. El csPCa fue definido como grado ISUP≥2.ResultadosLa incidencia de ASAP, mHGPIN y PIN-ATYP fue 4,2%, 39,7% y 3,7% respectivamente, y la tasa de csPCa fue estadísticamente similar en los pacientes con estos hallazgos histológicos. Sin embargo, las tasas de csPCa con atrofia proliferativa inflamatoria (PIA) presente y ausente fueron 22,2% y 36,1%, respectivamente. La PIA fue el único hallazgo histológico que predijo un menor riesgo de csPCa, con OR de 0,54 (IC 95%: 0,308-0,945, p=0,031). La PIA fue, también, un factor predictor independiente en un modelo combinando variables clínicas y mpMRI, que obtuvo un área bajo la curva de 0,86 (95% IC: 0,83-0,90).ConclusionesLa PIA resultó ser el único hallazgo histológico predictor del riesgo de csPCa, y puede contribuir en un modelo predictivo; mHGPIN no fue predictor de riesgo de csPCa. La baja incidencia de ASAP (4,2%) y PIN-ATYP (3,7%) impidió que pudiéramos obtener conclusiones sobre estas lesiones. (AU)

Introduction: Repeat prostate biopsy (PBx) is recommended under persistent suspicion of prostate cancer (PCa) or in the face of the following findings: atypical small acinar proliferation (ASAP), extense (≥3 biopsy sites) high-grade prostatic intraepithelial neoplasia (HGPIN), or HGPIN with atypical glands, suspicious for adenocarcinoma (PIN-ATYP). Nowadays, multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted PBx (MRI-TBx) are recommended in repeat PBx. Our objective was to analyze the current value of ASAP, mHGPIN, PIN-ATYP and other histological findings to predict clinically significant PCa (csPCa) risk.MethodsRetrospective analysis of 377 repeat PBxs. MRI-TBx was performed when Prostate Imaging-Reporting and Data System (PI-RADS) score>3 and 12-core transrectal ultrasound (TRUS) systematic PBx when≤2. ASAP, HGPIN, mHGPIN, PIN-ATYP, and 8 other histological findings were prospectively reported in negative PBx. CsPCa was defined as ISUP group grade>2.ResultsIncidence of ASAP, multifocal HGPIN (mHGPIN) and PINATYP was 4.2%, 39.7% and 3.7% respectively, and csPCa rate was statistically similar among men with these histological findings. However, the rate of csPCa was 22.2% when proliferative inflammatory atrophy (PIA) was present, and 36.1% when it was not. PIA was the only histological finding which predicted lower risk of csPCa, with an OR of .54 (95% CI: .308-.945, P=.031). In addition, PIA was an independent predictor of a model combining clinical variables and mpMRI which reached area under de ROC curve of .86 (95% CI: .83-.90).ConclusionsPIA emerged as the only predictive histological finding of csPCa risk and can contribute to a predictive model. mHGPIN failed to predict csPCa risk. The low incidence of ASAP (4.2%) and PIN-ATYP (3.7%) prevented us from drawing conclusions. (AU)

The current value of histological findings in negative prostate biopsies to predict the future risk of clinically significant prostate cancer.

BACKGROUND: Repeat prostate biopsy (PBx) is recommended under persistent suspicion of prostate cancer (PCa) or in the face of the following findings: atypical small acinar proliferation (ASAP); extense (≥3 biopsy sites) high-grade prostatic intraepithelial neoplasia (HGPIN); or HGPIN with atypical glands; suspicious for adenocarcinoma (PIN-ATYP). Nowadays; multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted PBx (MRI-TBx) are recommended in repeat PBx. Our objective was to analyze the current value of ASAP; mHGPIN; PIN-ATYP and other histological findings to predict clinically significant PCa (csPCa) risk. METHODS: Retrospective analysis of 377 repeat PBxs. MRI-TBx was performed when Prostate Imaging-Reporting and Data System (PI-RADS) score >3 and 12-core transrectal ultrasound (TRUS) systematic PBx when ≤2. ASAP; HGPIN; mHGPIN; PIN-ATYP; and 8 other histological findings were prospectively reported in negative PBx. CsPCa was defined as ISUP group grade >2. RESULTS: Incidence of ASAP; multifocal HGPIN (mHGPIN) and PINATYP was 4.2%; 39.7% and 3.7% respectively; and csPCa rate was statistically similar among men with these histological findings. However; the rate of csPCa was 22.2% when proliferative inflammatory atrophy (PIA) was present; and 36.1% when it was not. PIA was the only histological finding which predicted lower risk of csPCa; with an OR of 0.54 (95%CI: 0.308-0.945; P = .031). In addition; PIA was an independent predictor of a model combining clinical variables and mpMRI which reached area under de ROC curve of 0.86 (95%CI: 0.83-0.90). CONCLUSION: PIA emerged as the only predictive histological finding of csPCa risk and can contribute to a predictive model. mHGPIN failed to predict csPCa risk. The low incidence of ASAP (4.2%) and PIN-ATYP (3.7%) prevented us from drawing conclusions.

Rate of clinically significant prostate cancer on repeat saturation biopsy after a diagnosis of atypical small acinar proliferation.

BACKGROUND: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30%-40% of these patients may develop prostate cancer (PCa) within a 5-year period, often not clinically significant. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis, but it seem not to be the best strategy. METHODS: Objectives-evaluating the natural history of ASAP, stratifying the risk of csPCa after ASAP, identifying predictive factors of PCa after atypical diagnosis. Materials and methods-retrospective single-institutional study on patients undergoing prostate biopsy for suspicious PCa (2005-2016). We evaluated the incidence of overall PCa, intermediate-high risk of PCa and csPCa in case of ASAP, according to D'Amico classification and Epstein modified criteria. RESULTS: Out of 4.567 patients undergoing prostate biopsy, ASAP was detected in 2.6% of cases. All patients with ASAP underwent repeat saturation biopsy within 6 months and PCa was diagnosed in 34.5%. According to D'Amico classification, 26%, 5.9%, and 2.5% had low, intermediate, and high-risk disease, respectively. According modified Epstein criteria, the incidence of csPCa was 12.6%. LRT showed that the overall probability to develop PCa doubled when PSA density (PSAD) moved from values lower than 0.13 ng/ml/cc to class 0.13-0.30 ng/ml/cc, and it tripled when PSAD was higher than 0.30 ng/ml/cc. CONCLUSIONS: The rate of csPCa in patients with an initial diagnosis of ASAP who had repeat biopsy was 12.6%. The overall PCa rate was 34.5%. Among patient undergoing RP, an upgrading from ncsPCa to csPCa was reported in 35% of cases. PSAD is the only predictive factor directly associated to the risk of developing PCa on repeat biopsy. These findings suggest that immediate repeat biopsy remains the correct strategy in absence of novel predictor factors and non-invasive diagnostic evaluations.

Significance of atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia in prostate biopsy in China / 中华男科学杂志

Objective@#To assess the rates of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) detected in prostate biopsy in China and the risk of PCa found in subsequent repeat biopsy.@*METHODS@#A total of 2,456 patients underwent TRUS-guided prostate biopsy with the samples of ASAP and/or HGPIN tissues in our hospital at least twice between July 2014 and June 2019. We analyzed the findings of digital rectal examination, prostate volumes, PSA levels, and the results of prostate biopsies.@*RESULTS@#Initial prostate biopsies revealed 737 cases of PCa (30.0%), 215 cases of ASAP (8.8%), 98 cases of HGPIN (4.0%), and 18 cases of ASAP+HGPIN (0.7%). Totally, 313 of the patients met the inclusion criteria and included in this study. Of the 215 cases of ASAP confirmed in the first biopsy, 72 and 25 were diagnosed with PCa in the second and third biopsies, respectively, 83 with Gleason score (GS) 6, 14 with GS7, 57 with T1c and 40 with T2a tumors. Of the 98 cases of HGPIN confirmed in the first biopsy, 1 was diagnosed with PCa in the second and another 1 in the third biopsy, both with GS6 and T1c tumors. Of the 18 cases of ASAP+HGPIN confirmed in the first biopsy, 7 and 3 were diagnosed with PCa in the second and third biopsies, respectively, 7 with GS6, 3 with GS7, 6 with T1c and 4 with T2a tumors.@*CONCLUSIONS@#ASAP is a significant risk factor for PCa and repeat prostate biopsy should be performed for patients diagnosed with ASAP in the first biopsy. Whether repeat biopsy is necessary for those diagnosed with HGPIN depends on other related clinical parameters./.

Different clinical significance of ASAP/HGPIN pattern in systematic vs. MRI-US fusion guided prostate biopsy.

Atypical small acinar proliferation (ASAP) and high grade intraepithelial neoplasia (HGPIN) patterns identified at prostate biopsy yield an important clinical significance, their presence signaling an increased likelihood of future oncological development or underdiagnosed PCa. MRI and MRI-TRUS fusion prostate biopsy have recently become the standard for the diagnosis of prostate cancer. Thus, we aimed to assess the role of ASAP/HGPIN pattern in the context of these recent developments as compared with the standard systematic biopsy. The present study included 400 patients who underwent MRI-TRUS fusion prostate biopsy. A subgroup of these patients had a history of prior systematic biopsy and their results were also included in the analysis. We observed that ASAP/HGPIN pattern diagnosed at systematic biopsy is suggestive of a high-volume clinically-significant disease, most probably located outside the standard sampling area. On the contrary, ASAP/HGPIN at MRI-TRUS fusion biopsy has clinical features more similar to benign prostate hyperplasia, thus suggesting a more incipient disease, if present. No relation between concurrent ASAP/HGPIN and PCa was observed in our study.

Implementation of repeat biopsy and detection of cancer after a diagnosis of atypical small acinar proliferation of the prostate.

Current guidelines recommend a repeat biopsy within 3-6 months after an initial diagnosis of atypical small acinar proliferation (ASAP) due to the high incidence of cancer detection on repeat biopsy. The current study sought to investigate practice patterns after a diagnosis of ASAP in a real-world setting and examine the clinicopathological outcomes of repeat biopsy. The departmental database of the Hyogo Prefectural Nishinomiya Hospital identified 97 of 1,218 patients with a diagnosis of ASAP on initial biopsy from 2011 to 2016. Clinical and pathological data were retrospectively analyzed. Of the 97 patients, 34 (35.1%) underwent a repeat biopsy. Patients with a repeat biopsy had a significantly higher prostate-specific antigen (PSA) velocity and shorter PSA doubling time than patients without a repeat biopsy (P=0.0002), and of these 34 patients with a repeat biopsy, 16 (47.1%) were diagnosed as having cancer. Multivariate logistic regression analysis revealed that a small prostate (P=0.0250) and advanced age (P=0.0297) were associated with cancer detection on repeat biopsy. Of the 16 cancers identified, 13 (81.6%) were diagnosed with a Gleason score >6. The results indicated that the implementation of a repeat biopsy for patients with ASAP could be affected by clinical characteristics in real-world settings, despite the current recommendation of guidelines endorsing immediate repeat biopsy. Prostate volume and age would aid in the decision-making process to perform repeat biopsy in patients with high PSA velocity and short PSA doubling time after a diagnosis of ASAP.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

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

PURPOSE: Guidelines for atypical small acinar proliferation (ASAP) diagnosed on prostate biopsy recommend repeat biopsy within 3-6 months after diagnosis. We sought to discern the rate of detecting clinically significant prostate cancer on repeat biopsy and predictors associated with progression. MATERIALS AND METHODS: 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. RESULTS: 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 147 days (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: ß = - 0.12; P = 0.204). CONCLUSIONS: 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.

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.

The role of the serum testosterone levels as a predictor of prostate cancer in patients with atypical small acinar proliferation at the first prostate biopsy / 亚洲男科学杂志(英文版)

The current literature does not support the usefulness of clinical markers on predicting which patients with atypical small acinar proliferation (ASAP) are more likely to progress to prostate cancer (PCa). Androgens have long been considered to be the potential risk factors for PCa. However, the role of testosterone is controversial. The present study aims to analyze the relationship between serum testosterone (TS) levels and the diagnosis of PCa after a first prostate biopsy in patients affected by ASAP. This retrospective study included 143 patients diagnosed with ASAP in an initial transrectal ultrasound-guided prostate biopsy for suspicious PCa according to the European Association of Urology guidelines. Their TS levels, age, PSA, prostate volume, digital rectal examination, and prostate biopsy Gleason score (GS) were collected retrospectively for statistical analysis. All patients included in the study had a second biopsy and were suitable for further analysis. Re-biopsy was carried out 3-6 months after the first diagnosis of ASAP. Low and normal TS groups were composed of 29 (20.3%) and 114 (79.7%) patients, respectively. The diagnosis of the second biopsy was ASAP in 25.2% and PCa in 36.4% of patients. The comparison between patients with PCa and those with negative or an ASAP result in the second biopsy reported that men with cancer had significantly higher levels of TS (P < 0.001). However, there was no statistically significant association between GS postbiopsy and TS (P = 0.324). Our experience demonstrated that eugonadal patients may be a clinical risk factor for the diagnosis of PCa on re-biopsy after ASAP diagnosis than hypogonadal.

Atypical Small Acinar Proliferation and High Grade Prostatic Intraepithelial Neoplasia: Should We Be Concerned? An Observational Cohort Study with a Minimum Follow-Up of 3 Years.

INTRODUCTION: Atypical small acinar proliferation (ASAP) and high grade prostatic intraepithelial neoplasia (HGPIN) are considered precancerous. We aimed to measure the rate of repeat biopsy and adenocarcinoma in patients with ASAP and HGPIN and identify any clinico-pathologic parameters at diagnosis of ASAP/HGPIN that are predictive of adenocarcinoma. MATERIALS AND METHODS: Patients with a diagnosis of ASAP/HGPIN with no previous or concomitant cancer were identified. Prostate specific antigen (PSA) and magnetic resonance imaging (MRI) changes were monitored. Re-biopsy was at clinician discretion. RESULTS: Nineteen were diagnosed with ASAP and 17 with HGPIN. Seven with ASAP (37%) and 6 with HGPIN (35%) underwent re-biopsy. Three (16%) with ASAP and 5 with HGPIN (29%) were diagnosed with adenocarcinoma. The difference in cancer detection rates between ASAP and HGPIN was not significant (p = 0.35). Five (14%) in total required definitive therapy for adenocarcinoma. Twenty-three (64%) did not undergo repeat biopsy. Parameters at diagnosis of HGPIN and ASAP, including PSA, prostate volume and PSA density, were compared between the cancer and non-cancer cohorts with none found to be predictive of adenocarcinoma. CONCLUSION: By monitoring PSA and MRI changes, we managed to spare re-biopsy in two-thirds of patients. Further evaluation is necessary to characterize a surveillance protocol in these populations.

Atypical small acinar proliferation and two or more cores of high-grade intraepithelial neoplasia on a previous prostate biopsy are significant predictors of cancer during a transperineal template-guided saturation biopsy aimed at sampling one core for each 1 mL of prostate volume.

OBJECTIVE: The objective of this study was to evaluate whether high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) predict prostate cancer (PCa) during repeat transperineal template saturation biopsy with a high number of cores per prostate volume in patients with persistent clinical suspicion of PCa who underwent at least one previous negative transrectal ultrasound (TRUS)-guided biopsy. METHODS: We retrospectively evaluated 135 consecutive patients with persistent clinical suspicion of PCa, despite a set of negative TRUS-guided biopsies and increasing prostate-specific antigen levels; abnormal findings on digital rectal examination, TRUS, or magnetic resonance imaging; previous biopsy showing HGPIN; and previous biopsy showing atypical glands. Transperineal template saturation biopsy (TTSB) was performed at 5mm intervals to sample one core for each 1 mL of prostate volume. RESULTS: The median rate of biopsy cores per prostate volume was 1.00 (range: 0.75-1.39). The PCa detection rates in patients who were diagnosed with HGPIN, or had two or more cores of HGPIN or ASAP, were 53% (9/17), 89% (8/9), and 83% (10/12), respectively. Two or more HGPIN cores and ASAP were positive predictors of PCa on TTSB. The high-grade cancer rates (Gleason score [GS] ≥7) in patients with ASAP and two or more cores of HGPIN were 20% and 80%, respectively. The cancer detection rate represented by a GS score ≥8 in patients with ASAP or two or more cores of HGPIN at a previous TRUS-guided biopsy was 5.5% (1/18). CONCLUSION: ASAP or two or more cores of HGPIN at a previous TRUS-guided biopsy strongly indicated the presence of PCa on TTSB.

Immunohistochemistry in the workup of prostate biopsies: Frequency, variation and appropriateness of use among pathologists practicing at an academic center.

OBJECTIVES: We studied the frequency, inter-pathologist variation, appropriateness and utility of immunohistochemistry (IHC) performed on prostate biopsies (PB) to determine the significance of foci of suspicious glands/atypical small acinar proliferations (ASAP). METHODS: We calculated the rate of IHC use and diagnostic rate of ASAP and adenocarcinoma in PB from 01/01/2008 to 06/30/2015 for individual pathologists working in a tertiary academic institution, and correlated them with the pathologists' experience, subspecialization and PB volume with the aim of determining the interpathologist variation and appropriateness of use of IHC according to recently published recommendations, and the usefulness of IHC to resolve foci of ASAP as either benign or adenocarcinoma. RESULTS: IHC was used in 966/2652 (36.4%, 95% CI 33.4-39.4%) PB cases and 1915 of 16,359 (11.7%, 95% CI 11.2%-12.2%) of PB blocks and allowed definitive diagnosis of either benign or malignant in 75.8% (95% CI 73.9-77.7%) of blocks. By pathologist, IHC use rates varied more than twofold (22.8-50.5%); higher use was found for pathologists with genitourinary pathology specialization, higher PB volume and more experience, and correlated with higher rates of both ASAP and adenocarcinoma diagnoses. The use of IHC stains was considered appropriate in 822/966 (85.1%, 95% CI 82.9-87.4%) cases. CONCLUSIONS: Despite the fact that the use of IHC stains was considered useful and deemed appropriate in the majority of cases, it showed wide variation between pathologists, suggesting monitoring of IHC use rates may be useful to standardize its use.

Incidence, grade and distribution of prostate cancer following transperineal template-guided mapping biopsy in patients with atypical small acinar proliferation.

PURPOSE: To evaluate the role of transperineal template-guided mapping biopsy (TTMB) in patients with atypical small acinar proliferation (ASAP) diagnosed via transrectal ultrasound-guided needle biopsy (TRUS). METHODS: In total, 132 consecutive patients with TRUS-diagnosed ASAP underwent TTMB by means of an anatomic-based technique with sampling of 24 biopsy regions. For each of the 24 regions, 1-3 biopsy cores were obtained (depending on prostate size). No patient underwent pre-biopsy MRI imaging. The Gleason score, location of each positive biopsy core, the number of biopsy cores and percent involvement of each core were recorded. Anterior versus posterior cancer distribution was determined for both low- and high-grade (Gleason score ≥7) cancer. RESULTS: The mean patient age was 63.8 years with a mean PSA of 6.8 ng/mL. Of the 132 patients, 86 (65.2%) were diagnosed with prostate cancer. Of the entire cohort, 47 patients (54.7% of cancer patients and 35.6% of the entire cohort) were diagnosed with Gleason score ≥7. For both low- and high-grade cancers, the anterior gland and especially the anterior apex were the most common cancer locations. CONCLUSION: In patients with ASAP, TTMB diagnosed prostate cancer in 65.2% of patients and 35.6% of the entire cohort had high-grade prostate cancer. A predilection for anterior-based cancers, especially the anterior apex, was identified. Our study may serve as a baseline reference for MRI-guided biopsy regimens.