Avaliação de fatores de risco e antígeno prostático específico no rastreamento de câncer de próstata / Evaluation of risk factors and prostate-specific antigen in prostate cancerscreening

Introdução: no Brasil, o câncer de maior incidência nos homens é o câncer de próstata (CaP), com 6,9% de mortalidade. Atualmente, discute-se a aplicabilidade do antígeno prostático específico (PSA) em políticas de rastreamento para CaP e os riscos associados ao sobrediagnóstico. Objetivo: correlacionar a dosagem do PSA com fatores de risco, história clínica e a presença de neoplasia prostática. Metodologia: estudo descritivo transversal que analisou, comparativamente, dados clínico-epidemiológicos e níveis séricos de PSA de 200 pacientes. Valores de PSA foram estratificados em três categorias (<2,5, 2,5­10,0 e >10 ng/ml). Resultados: os fatores de risco analisados foram relacionados significativamente com o aumento do PSA e neoplasia prostática. A prevalência de CaP (11%) e hiperplasia prostática (61%) foi observada nos pacientes com maior dosagem de PSA, enquanto 1% dos pacientes apresentou CaP sem alteração do PSA e 4% tiveram CaP com 2,5­10,0 ng/ml de PSA. Maiores níveis séricos do biomarcador foram relacionados a diabetes (70%), hipertensão (77%), uso crônico de medicações (60%) e ausência de exames periódicos (58%). O grupo com PSA >10 ng/ml teve média de idade maior que o primeiro (p = 0,002) e o segundo grupos (p = 0,027). Conclusão: a prevalência de hiperplasia prostática benigna associada à alteração do PSA, e o elevado risco de exames falso-positivos evidenciam a preocupação com o sobrediagnóstico. No contexto dos dados clinico-epidemiológicos avaliados, a possibilidade de resultados falso-positivos e falso-negativos associados à dosagem do PSA deve ser considerada, ressaltando a importância de adoção de exames complementares para rastreio do CaP.

Introduction: in Brazil, the cancer with the highest incidence in men is prostate cancer (PCa), with 6.9% mortality. Currently, the applicability of prostate specific antigen (PSA) in screening policies for PCa and the risks associated with overdiagnosis are discussed. Objective: to correlate the PSA level with risk factors, clinical history and the presence of prostatic neoplasm. Methods: a cross-sectional descriptive study that analyzed, comparatively, clinical-epidemiological data and serum PSA levels of 200 patients. PSA values were stratified into three categories (<2.5, 2.5­10.0 and> 10 ng / ml). Results: the risk factors analyzed were significantly related to the increase in PSA and prostatic neoplasm. The prevalence of PCa (11%) and prostatic hyperplasia (61%) was observed in patients with higher levels of PSA, while 1% of patients had PCa without PSA changes and 4% had PCa with 2.5­10.0 ng/ml PSA. Increased serum levels of the biomarker were related to diabetes (70%), hypertension (77%), chronic use of medications (60%) and periodic exams (58%). The group with PSA> 10 ng/ml had a mean age greater than the first (p = 0.002) and the second group (p = 0.027). Conclusion: the prevalence of benign prostatic hyperplasia associated with PSA change and an increased risk of false-positive tests show a concern with overdiagnosis. In the context of clinical-epidemiological data, the possibility of false-positive and false-negative results associated with the PSA measurement have to be considered, highlighting the importance of complementary tests for PCa screening.

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./.

CIP2A expression in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue microarray study

@#CIP2A is an oncoprotein involved in the progression of several human malignancies. It has recently been described as a prognostic marker in many cancers. The present study aimed to investigate the immunohistochemical expression of CIP2A in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse the association with the clinicopathological parameters in PC cases to define its role in the development and progression of PC. Materials and Methods: Immunohistochemical staining for CIP2A was performed on the tissue microarray sections of 105 PC, 27 HGPIN and 27 BPH tissues. The CIP2A expression scores were compared with several clinicopathological parameters. Results: CIP2A was expressed in 96,2% of PC, 55,6% of HGPIN and 40,7% of BPH tissues. The expression of CIP2A in PC was significantly higher than in HGPIN (p<0.0001) and BPH (p<0.0001) cases. CIP2A expression score was significantly associated with Gleason score (p=0.032) and lymphovascular invasion (p=0.039). Nevertheless, there was no statistically significant association between the expression of CIP2A and perineural invasion, pT stage, metastasis and recurrence (p>0.05). Multivariate analysis indicated that GS, lymphovascular invasion, distant metastasis were independent prognostic factors for PC patients but, CIP2A expression score was not found to be a prognostic factor. Additionally, there was no significant difference between the survival times of patients according to CIP2A expression (p=0.174). Conclusion: According to our results, the expression of CIP2A protein is increased in PC and its expression may be involved in the development, differentiation, and aggressiveness of PC. However, further studies are needed to confirm our findings and to clarify the role of CIP2A in the development of PC.

Recommendations of Test of Prostate-specific Antigen along with Histopathological Examination for the Prostate Lesions

Introduction: Prostate disease is an important growing health problem, presenting a challenge to urologists, radiologists, and pathologists. Objectives: The aim of the study is to correlate prostatic-specific antigen test with histopathological examination in prostatic lesions and to recommend combine approach for management of the patients of prostatic lesions. Materials and Methods:This was a prospective study conducted at the department of pathology in a tertiary care center over 6 months. Data were collected from histopathology record department. The 2002 WHO classification was used to diagnose and classify prostate tumors. Gleason’s grading system was used for the cases of adenocarcinoma. Results: In our study, a total of 119 cases of prostatic lesions were noticed. The lesions diagnosed were benign prostatic hyperplasia (79% of cases), adenocarcinoma (6% of cases), prostatic intraepithelial neoplasia (4% of cases), stromal nodules of hyperplasia (4% of cases), and atypical adenomatous hyperplasia (4% of cases). A total of 3% of cases were inadequate. Majority of prostatic lesions were belonging to the 6th decade followed by the 7th decade. All cases of adenocarcinoma were belonging to the 6th decade. The test of prostatic-specific antigen was higher (more than 10 ng) in cases of adenocarcinoma. Conclusions: The study is conducted to see that combine approach of prostate-specific antigen and histopathological examination is useful for its recommendation, for better management of prostatic lesions in tertiary care center.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice

BACKGROUND: Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. METHODS: Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. RESULT: In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. CONCLUSION: Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (p<0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Development of prostate cancer risk in patients with chronic prostate inflammation and wHGPIN during puncture rebiopsy / 实用肿瘤学杂志

Objective The objective of this study was to investigate a risk of prostate cancer(PCa) at a repeat biopsy in patients with chronic prostate inflammation and widespread high grade prostatic intra epithelial neoplasia(wHGPIN).Methods From July 2006 to December 2014,172 cases of prostate biopsy were collected.All of them were diagnosed as HGPIN for the first biopsy,punctured by transrectal ultrasound for 12 points.After the first puncture for 6 months,patients were punctured for rebiopsy.Multi-focal wHGPIN was defined as a high -grade prostate intraepithelial neoplasia with 2 or more cores detection in a prostate biopsy.Isolated HGPIN was defined as a high-grade prostate intraepithelial neoplasia with only one core detection in a prostate biopsy.Results Seventy-two patients with HGPIN were isolated from primary HGPIN,102 patients with isolated HGPIN,17 patients with chronic prostatitis,70 with multifocal HGPIN and 54 with chronic prostatitis.Forth-eight of 172 patients initial diagnosis of HGPIN was diagnosed as PCa at rebiopsy.The detection rate of wHGPIN was 52.86％ (37/70)and isolated HGPIN for 10.88％ (11/102).They showed a statistically difference between two groups(P ＜0.001).The detection rate of PCa in HGPIN patients with chronic prostatitis was higher than that in patients without chronic prostatitis(P =0.011).Chronic prostatitis and multifocal wHGPIN were a risk factor for prostate cancer independent by rebiopsy,confirmed by the logistic regression model.Conclusion Rebiopsy is a high risk factor of prostate adenocarcinoma for patients with chronic prostatitis and multifocal HGPIN initially diagnosed by the first biopsy.Therefore,these patients are recommended under ultrasound induced by rectal prostate rebiopsy.

ESTANDARIZACIÓN DEL PROTOCOLO PARA LA DETECCIÓN DE LAS FUSIONES TMPRSS2: ERG Y DE LA EXPRESIÓN DE LOS GENES EZH2, SPINK-1 y NKX3.1 EN CÁNCER DE PRÓSTATA (CaP) / Protocol Standardization for Detection of TMPRSS2 Fusions: ERG and Gene Expression of EZH2, SPINK-1 and NKX3.1 in Prostate Cancer (PCa)

En la actualidad no existe una herramienta que permita diferenciar pacientes con cáncer de próstata (CaP) de mal pronóstico de aquellos con enfermedad indolente que sólo requieren un seguimiento controlado de la enfermedad. Debido a la coexistencia de diferentes focos premalignos y malignos en el CaP, el entendimiento sobre el proceso de carcinogénesis requiere de un mejor conocimiento. Actualmente, la heterogeneidad morfológica en CaP es evaluada con la puntuación de Gleason, la cual está fuertemente relacionada con el pronóstico de la enfermedad, sin embargo, esto es insuficiente por lo que se trabaja actualmente en identificación de alteraciones moleculares que permitan identificar subtipos que puedan establecer de manera más precisa el pronóstico del paciente. Este estudio preliminar buscó la estandarización del método de cuantificación en muestras prostáticas de FFPE de la expresión de los transcritos de posibles biomarcadores, como los oncogenes SPINK-1 y EZH2, el supresor tumoral NKX3.1, en conjunto con la determinación de la presencia/ausencia del gen de fusión TMPRSS2:ERG, ya que estos transcritos se encuentran involucrados en aparentes eventos excluyentes de la evolución natural del CaP, que apoyan la posibilidad de una clasificación molecular para esta enfermedad.

At present doesn't exist tool to differentiate patients with prostate cancer (PCa) of poor prognosis of those with indolent disease that only require a controlled monitoring of the disease. Because of the coexistence of different premalignant and malignant foci in CaP, the understanding of the carcinogenesis process requires a better understanding. Currently, the morphological heterogeneity in PCa is evaluated with Gleason score, which is closely related to the prognosis of the disease, but this is insufficient so it is currently to work on identifying molecular alterations to identify subtypes that can establish more precisely the patient's prognosis. This preliminary study aimed to standardization of the method of quantification in prostatic samples of FFPE of expression of transcripts of possible biomarkers, such as the oncogenes, SPINK-1 y EZH2, the tumour suppressor, NKX3.1, together with the determination of the presence/absence of gene fusion, TMPRSS2:ERG, being that these transcripts are involved in apparent exclusive events of the natural evolution of PCa, that support the possibility of a molecular classification for this disease.

Intraductal Carcinoma of the Prostate Gland: Recent Advances

Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up.

Clinical features and prognosis of prostate cancer with high-grade prostatic intraepithelial neoplasia

PURPOSE: To evaluate the clinical features and biochemical recurrence (BCR) in prostate cancer (PCa) with high-grade prostatic intraepithelial neoplasia (HGPIN). MATERIALS AND METHODS: We retrospectively analyzed the medical records of 893 patients who underwent a radical prostatectomy for PCa between 2011 and 2012 at Asan Medical Center; 752 of these patients who did not receive neoadjuvant or adjuvant therapy and were followed up for more than 1 year were included. The cohort was divided into two groups-patients with and without HGPIN-and their characteristics were compared. The Cox proportional hazards model was used to analyze factors affecting BCR. RESULTS: In total, 652 study patients (86.7%) had HGPIN. There were no significant differences in preoperative factors between the two groups, including age (p=0.369) and preoperative prostate-specific antigen concentration (p=0.234). Patients with HGPIN had a higher Gleason score (p=0.012), more frequent multiple tumor (p=0.013), and more perineural invasion (p=0.012), but no other postoperative pathologic characteristics were significantly different between the two groups. There were no significant differences in BCR (13.0% vs. 11.5%, p=0.665) and HGPIN was not associated with BCR (p=0.745). In multivariate analysis, only the T stage (p<0.001) was associated with BCR. CONCLUSIONS: PCa patients with HGPIN have a higher Gleason score, more frequent multiple tumors, and more perineural invasion than those without HGPIN. The presence of HGPIN is not an independent predictor of BCR.

Multiple cores of high grade prostatic intraepithelial neoplasia and any core of atypia on first biopsy are significant predictor for cancer detection at a repeat biopsy

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.

How many cores should be taken in a repeat biopsy on patients in whom atypical small acinar proliferation has been identified in an initial transrectal prostate biopsy?

Objective To compare cancer detection rates according to the number of biopsy cores in patients on whom a repeat prostate biopsy was performed for atypical small acinar proliferation (ASAP). Materials and Methods The data of 4950 consecutive patients on whom prostate biopsies were performed were assessed retrospectively. A total of 107 patients were identified as having ASAP following an initial prostate biopsy, and they were included in the study. A six-core prostate biopsy (PBx) was performed on 15 of the 107 patients, 12 PBx on 32 patients, and 20 PBx on 60 patients. Cancer detection rates were compared according to the number of biopsy cores. The localization of the cancer foci was also evaluated. Results The cancer detection rates in patients on whom 6 PBx, 12 PBx, and 20 PBx were performed were 20% (3/15), 31% (10/32), and 58% (35/60), respectively, and a statistically significant difference was found (p = 0.005). When cancer detection rates in patients with total prostate specific antigen (PSA) < 10ng/mL, PSA density ≥ 0.15, normal digital rectal examination, and prostate volume ≥ 55mL were compared according to the number of biopsy cores, a significant difference was identified (p = 0.02, 0.03, 0.006, and 0.04, respectively). Seventy-five percent of the foci where cancer was detected were at the same and/or adjacent sites as the ASAP foci in the initial biopsy, and 54% were identified in contralateral biopsies in which ASAP foci were present. Conclusion As the biopsy core number increases, the cancer detection rate increases significantly in patients on whom a repeat biopsy is performed due to ASAP. The highest cancer rate is found in 20-core repeat biopsies performed equally from all foci. .

Study of High Grade Prostatic Intraepithelial Neoplasia for a Period of Five Years

A relatively new development in the arena of prostatic histopathological study is the premalignant proliferative high grade prostatic intraepithelial neoplasia (HGPIN) in the glandular epithelium, possibly relating to carcinoma. Aim of the study is HGPIN and its association with Prostatic hyperplasia and Prostatic carcinoma. The present study was undertaken in the Upgraded Department of Pathology, King George Hospital, Andhra Medical College for a period of five years from January 2002 to December 2006. A total of 340 cases evaluated, 277 (81.47%) were benign, 11 (3.23%) were premalignant and 52 (15.29%) malignant lesions. Premalignant lesions were preceded by a decade as compare to malignant lesions, with a mean age of 8 years difference. Among premalignant lesions only high grade prostatic intraepithelial lesion is seen in association with prostatic carcinoma (40%).

Matrix metalloproteinases 2 and 9 expression in canine normal prostate and with proliferative disorders / Expressão de metaloproteinases de matriz 2 e 9 na próstata canina normal e com lesões proliferativas

In this study the expression of metalloproteinases 2 (MMP-2) and 9 (MMP-9) in canine normal prostates and with proliferative disorders was evaluated to verify the role of these enzymes in extracellular matrix remodeling (ECM) and in the tissue invasion process. A total of 355 prostatic samples were obtained, from which 36 (10.1%) were normal prostates, 46 (13.0%) with benign prostatic hyperplasia (BPH), 128 (36.1%) with proliferative inflammatory atrophy (PIA), 74 (20.8%) with prostatic intraepithelial neoplasia (PIN), and 71 (20.0%) with prostatic carcinoma (PC). Difference in cytoplasmic immunohistochemical staining of MMP-2 and MMP-9 between acinar epithelium and periacinar stroma was found regarding the different diagnosis. The correlation between MMP-2 and MMP-9 expression in relation to the number of labeled cells in acinar epithelium and periacinar stroma, as well as to the staining intensity in the periacinar stromal cells was evidenced in canine prostates with PIA. In conclusion, MMP-2 and MMP-9 expression has a variation in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in those with PIA, PIN and PC. Moreover, the inflammatory microenvironment of the PIA has influence in the activity of both enzymes.

Este estudo teve como objetivo avaliar a expressão das metaloproteinases 2 (MMP-2) e 9 (MMP-9) em próstatas caninas normais e com desordens proliferativas, verificando o papel dessas enzimas na remodelação da matriz extracelular (MEC) e no processo de invasão tecidual. Um total de 355 amostras prostáticas foram obtidas, sendo 36 (10,1%) normais, 46 (13,0%) com hiperplasia prostática benigna (HPB), 128 (36,1%) com atrofia inflamatória proliferativa (PIA), 74 (20,8%) com neoplasia intraepitelial prostática (PIN) e 71 (20,0%) com carcinoma prostático (CP). Houve diferença de imunomarcação citoplasmática para MMP-2 e MMP-9 entre o epitélio acinar e o estroma periacinar, quanto aos diferentes diagnósticos. Observou-se correlação entre a expressão de MMP-2 e MMP-9 em relação ao número de células marcadas no epitélio acinar e estroma periacinar, bem como para a intensidade de marcação das células estromais periacinares em próstatas caninas com PIA. Conclui-se que há variação na expressão de MMP-2 e MMP-9 em próstatas caninas de acordo com a lesão, com menor expressão em próstatas caninas normais e com HPB, e maior naquelas com PIA, PIN e CP. Ainda, o microambiente inflamatório na PIA influencia a atividade de ambas as enzimas.

The feature and clinical significance of serum PSA and PSAD in patients with prostatic intraepithelial neopiasia / 中华泌尿外科杂志

Objective To investigate the serum prostate specific antigen tPSA),ratio of serum free PSA to total PSA (f/t),prostate volume (PV) and prostate specific antigen density (PSAD),their correlation with prostatic intraepithelial neoplasia (PIN) and their clinical diagnostic significance. Methods Retrospectively evaluate 165 cases of patients with PIN ( including 31 cases of LGPIN,134 cases of HGPIN),which confirmed by pathology,and 252 cases of benign prostatic hyperplasia (BPH),49 patients with prostate cancer (PCa),both diagnosed by pathology,as control.The average age of BPH,LGPIN,HGPIN,PCa groups were 70.13 ± 0.43,70.97 ± 1.28,70.74 ± 0.64,70.37 ± 1.40,the International Prostate Symptom Score (IPSS) were 20.20 ± 0.88,14.71 ± 3.42,20.19 ± 1.239,19.27 ± 2.73,and the PV were 58.07 ± 3.58,56.01 ± 7.52,60.74 ± 4.81,47.56 ± 6.54,respectively.The data of PSA,f/t,PV and PSAD were analyzed and compared within the four groups. Results Age,IPSS score and PV had no significant difference among the four groups (P ＞ 0.05).The PSA level of BPH,LGPIN,HGPIN,PCa groups were 5.65 ±0.38,5.86 ±0.81,8.91 ±0.71,13.80 ±1.83,the f/t ratio were 0.26 ±0.01,0.24 ±0.02,0.22 ±0.01,0.167 ± 0.01,and the PSAD level were 0.11 ± 0.01,0.10 ± 0.02,0.19 ±0.03,0.48 ±0.12,respectively.PSA,f/t and PSAD were not significantly different between HGPIN and LGPIN ( P ＞ 0.05 ),and likewise between LGPIN and BPH patients ( P ＞ 0.05 ).PSA,f/t and PSAD were significantly different between LGPIN and PCa patients ( P ＜ 0.05),and likewise between HGPIN and BPH patients (P ＜ 0.05 ).PSA and PSAD were significantly different between HGPIN and PCa (P ＜ 0.05 ).The areas under the ROC curve of PSA and PSAD of HGPIN were 0.6281 (P ＜0.01 ) and 0.5919 (P ＜0.05).Conclusions PSA and PSAD are correlated with HGP1N and can predict the existence of HGPIN early;PSAD can identify HGPIN and PCa,when PSA and f/t are normal.The clinical features of LGPIN are similar to BPH,and HGPIN is easy to develop to PCa.

High-Grade Prostatic Intraepithelial Neoplasia

High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.

Serum PSA level in prostatic lesions with histopathological correlation in Gujarat.

Background: Prostate specific antigen (PSA) has been widely used in the diagnosis and management of patients with prostate cancer. It may be elevated in other prostatic diseases and surgical procedures. PSA exists in two forms, a major bound form (cPSA) and a free form (fPSA). Objectives: The objective of the study was to determine the relationship between serum fPSA levels and histologic findings in biopsy specimens of men with prostatic disease. Material and methods: This study includes 80 cases of prostatic diseases and 20 controls for the study were taken from the patients admitted in surgical wards with no prostate related complain, in different age were planned for transurethral resection of prostate (TURP). All the cases and controls were evaluated by serum prostate specific antigen level. Results: The median serum fPSA values for control, malignant and nonmalignant lesions were 3.66 ± 0.029 ng/ml, 20.33 ± 0.0106 ng/ml and 6.47 ± 0.8127 ng/ml respectively. Mean serum PSA values in cases of prostatic hyperplasia with or without dysplasia (PIN: Prostatic Intraepithelial Neoplasia I to III), prostatitis, well to moderately differentiated adenocarcinoma and poorly differentiated adenocarcinoma were 6.49 ng/ml, 5.35 ng/ml, 18.92 ng/ml and 31.6 ng/ml respectively. Cut off value of serum PSA 4 ng/ml the sensitivity, specifically and positive predictive value were 100 % and 14.28 % respectively while using 10 ng/ml the findings were 77.77 %, 92.95% and 58.33% respectively. Difference is highly significant between control cases and nonmalignant cases, (p < 0.001) as well as between nonmalignant cases and malignant cases (p < 0.001). Conclusions: In cases of prostatic hyperplasia, chronic prostatitis and prostatic malignancy serum fPSA value increases significantly (P < 0.001) above the standard (0 to 4 ng/ml) as compare to control and nonmalignant group. Statistically there is significant difference in serum fPSA values between control cases and non malignant cases as well between nonmalignant cases and malignant cases of prostate, but when serum PSA values are between 4.0 to10.0 ng/ml.

The implication of initial 24-core transrectal prostate biopsy protocol on the detection of significant prostate cancer and high grade prostatic intraepithelial neoplasia

PURPOSE: To assess the diagnostic value of an initial 24-sample transrectal ultrasound guided (TRUS) prostate biopsy protocol compared to the 10-core technique. MATERIALS AND METHODS: We retrospectively reviewed the prostate biopsy database of consecutive men undergoing prostate biopsies under local anesthesia by using the 10 (Group A) and 24 (Group B) protocols. Men were stratified according to biopsy protocol and PSA levels. Exclusion criteria were age = 75 years and PSA > 20 ng/mL. The Mann-Whitney U and Fisher's exact test were used for statistical analysis. RESULTS: Between April 2007 and August 2009, 869 men underwent TRUS prostate biopsies of which 379 were eligible for the study. Group A (10-cores) consisted of 243 (64.11 percent) men and group B (24-cores) included 139 (35.89 percent) men. The overall prostate cancer detection rate was 39.09 percent and 34.55 percent in Group A and B, respectively (p = 0.43). An overall 9.8 percent increase in Gleason 7 detection rate was found in Group B (p = 0.24). The high-grade prostatic intraepithelial neoplasia (HGPIN) detection rate in men with negative initial biopsies was 15.54 percent and 35.55 percent in Group A and B, respectively (p < 0.001). In patients with PSA < 10 ng/mL, the 24-core technique increased Gleason 7 detection rate by 13.4 percent (p = 0.16) and HGPIN by 23.4 percent (p = 0.0008), compared to the 10 core technique. The 24-core technique increased the concordance between needle biopsy and prostatectomy specimen compared to 10-core technique (p < 0.002). CONCLUSIONS: The initial 24-core prostate biopsy protocol did not show any benefit in the detection of prostate cancer compared to the 10-core technique. However, it improved the HGPIN detection and the correlation between biopsy results and radical prostatectomy Gleason score in men with lower PSA levels.

Significance of Atypical Small Acinar Proliferation and High-Grade Prostatic Intraepithelial Neoplasia in Prostate Biopsy

PURPOSE: In clinical practice, atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two common findings on prostate biopsies. Knowing the frequency of a prostate cancer diagnosis on repeat biopsies would aid primary treating physicians regarding their decisions in suspicious cases. MATERIALS AND METHODS: One hundred forty-three patients in whom biopsies revealed ASAP or HGPIN or both were enrolled in the present study; prostate cancer was not reported in the biopsy specimens and at least one repeat biopsy was performed. Age, digital rectal examination findings, prostate volumes, and free and total prostate-specific antigen (PSA) levels and the biopsy results of the patients were recorded. RESULTS: Of the 97 patients with ASAP on the first set of biopsies, prostate cancer was diagnosed in the second and third biopsies of 32 and 6 patients, respectively. Prostate cancer was not detected in the second or third biopsies of the 40 patients with HGPIN in the first biopsy. Of the 6 patients with ASAP+HGPIN in the first biopsy, prostate cancer was detected in 3 patients in the second biopsy and in 1 patient in the third biopsy. CONCLUSIONS: The diagnosis of ASAP is a strong risk factor for prostate cancer. A repeat biopsy should be performed for the entire prostate subsequent to the diagnosis of ASAP. In patients with HGPIN according to the biopsy result, the clinical decision should be based on other parameters, such as PSA values and rectal examination, and a repeat biopsy should be avoided if the initial biopsy was performed with multiple sampling.

Clinical Predictive Factors in Patients with Prostate Cancer Diagnosed by Repeat Prostate Biopsy / 대한남성과학회지

PURPOSE: We investigated the predictive factors in patient with prostate cancer diagnosed by repeat prostate biopsy, where initial prostate biopsy results were negative for malignancy. MATERIALS AND METHODS: Between March 2000 and June 2007, 1280 men with suspected prostatic cancer underwent transrectal ultrasound guided needle biopsy of the prostate, with 148 (11.6%) diagnosed as having prostate cancer. Of 1132 men whose biopsy results were negative for malignancy, 655 whose prostate specific antigen (PSA) was elevated persistently underwent second biopsy, and 462 underwent third biopsy as the same course. Twelve core biopsies were performed in the majority of patients. To determine predictive factors, we evaluated prostate volume, serum PSA, percent free PSA, PSA density (PSAD), transition zone PSAD, PSA velocity (PSAV) and pathological report of previous biopsy between the men with cancer detection and the men with negative biopsy in second and third biopsy. RESULTS: Overall cancer detection rate was 16.3% (208/1280). From the first, second and third biopsies, the cancer detection rate were 11.6, 5.5 and 5.2%, respectively. There were significant differences in percent free PSA, transition zone PSAD, PSAV between cancer and negative biopsy groups after serial repeat biopsies (p<0.05). Multivariate logistic regression analysis revealed that the transition zone PSAD, PSAV, and presence of either atypical small acinar proliferation (ASAP) or high grade prostatic intraepithelial neoplasia (HGPIN) in initial biopsy specimen were significant predictors for prostate cancer diagnosed by repeat biopsy. CONCLUSIONS: Of the men with negative results on the first biopsy, 60 (5.4%) were diagnosed prostate cancer after serial biopsies. The transition zone PSAD, PSAV, and presence of either ASAP or HGPIN in initial biopsy specimen are predictable factors for prostate cancer detection on repeat biopsy.