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1.
Diagnostics (Basel) ; 13(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37685317

RESUMO

This study aimed to develop a noninvasive Machine Learning (ML) model to identify clinically significant prostate cancer (csPCa) according to Gleason Score (GS) based on biparametric MRI (bpMRI) radiomic features and clinical information. METHODS: This retrospective study included 86 adult Hispanic men (60 ± 8.2 years, median prostate-specific antigen density (PSA-D) 0.15 ng/mL2) with PCa who underwent prebiopsy 3T MRI followed by targeted MRI-ultrasound fusion and systematic biopsy. Two observers performed 2D segmentation of lesions in T2WI/ADC images. We classified csPCa (GS ≥ 7) vs. non-csPCa (GS = 6). Univariate statistical tests were performed for different parameters, including prostate volume (PV), PSA-D, PI-RADS, and radiomic features. Multivariate models were built using the automatic feature selection algorithm Recursive Feature Elimination (RFE) and different classifiers. A stratified split separated the train/test (80%) and validation (20%) sets. RESULTS: Radiomic features derived from T2WI/ADC are associated with GS in patients with PCa. The best model found was multivariate, including image (T2WI/ADC) and clinical (PV and PSA-D) information. The validation area under the curve (AUC) was 0.80 for differentiating csPCa from non-csPCa, exhibiting better performance than PI-RADS (AUC: 0.71) and PSA-D (AUC: 0.78). CONCLUSION: Our multivariate ML model outperforms PI-RADS v2.1 and established clinical indicators like PSA-D in classifying csPCa accurately. This underscores MRI-derived radiomics' (T2WI/ADC) potential as a robust biomarker for assessing PCa aggressiveness in Hispanic patients.

2.
Mol Clin Oncol ; 15(3): 185, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34277004

RESUMO

During initial risk assessments, the metastatic potential of prostate cancer (PCa) may not be fully considered. The tumor's multicentric origin, which is associated with genetic mutations, may explain existing treatment limitations. Investigating human epidermal growth factor receptor 2 (HER2) expression in patients with different stages of PCa may therefore increase understanding of the mechanisms associated with the development of castration resistance. The present study examined the association between HER2 expression and the histologic features of PCa subjected to radical prostatectomy (RP) and evaluated the role of testosterone suppression in HER2 expression. In group 1, specimens from individuals who underwent RP without prior neoadjuvant androgen deprivation therapy (ADT) were included (n=42). In group 2 (PCa with ADT), specimens from individuals who underwent RP and received neoadjuvant cyproterone acetate during distinct periods (200 mg daily for 1-24 months) were included (n=150; cohort derived from a previous study). Immunohistochemical expression of HER2 was associated with prognostic factors such as perineural invasion, extra-prostatic disease, T stage, serum prostate-specific antigen (PSA), angiolymphatic invasion and surgical margins. Univariate regression analysis indicated that perineural invasion, PSA, International Society of Urological Pathology, angiolymphatic invasion, margin, T stage and neoadjuvant ADT was associated with HER2 expression. Ordinal regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (P<0.001). In addition, regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (odd ratio=0.01; 95% CI, 0.00, 0.02; P<0.001). HER2 was expressed in PCa samples but was not associated with known prognostic factors. The use of short-acting ADT and the consequent blockage of testosterone effect may suppress the expression of HER2 in PCa cells.

3.
Urol Oncol ; 39(12): 831.e11-831.e18, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34193378

RESUMO

BACKGROUND: Prostate cancer screening has reduced its mortality in 21%. However, this has also led to an increased number of biopsies in order to establish the diagnosis, many of them unnecessary. Current screening guidelines prioritize use of prostatic magnetic resonance and new biomarkers to reduce unnecessary biopsies, however, their implementation in developing countries screening programs is mainly limited by its costs. OBJECTIVE: We aimed to evaluate Prostate Biopsy Risk Collaborative Group (PBCG) and Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) 2.0 predictions accuracy in Mexican patients in order to guide prostate biopsy decision making and reduce unnecessary biopsies. MATERIALS AND METHODS: We retrospectively analyzed patients between 55 and 90 years old who underwent prostate biopsy in a high-volume center in Mexico between January 2017 and June 2020. Clinical utility of PBCG and PCPTRC 2.0 to predict high-grade prostate cancer (HGPCa) biopsy outcomes was evaluated using decision curve analysis and compared to actual biopsy decision making. Receiver operating characteristics area under the curve (AUC) was used to measure discrimination and external validation. RESULTS: From 687 patients eligible for prostate biopsy, 433 met selections criteria. One hundred and thirty-five (31.17%) patients were diagnosed with HGPCa, 63 (14.54%) with low-grade disease and 235 (54.27%) had a negative biopsy. PCPTRC 2.0 ≥15% threshold got a standardized net benefit (sNB) of 0.70, while PBCG ≥30% and ≥35% had a sNB of 0.27 and 0.15, respectively. Use of both models for guiding prostate biopsy decision resulted in no statistical difference for HGCPa detection rates, while achieved a significant difference in reducing total and unnecessary biopsies. However, this difference was lower (better) for PCPTRC 2.0, being statistically significative when compared against PBCG thresholds. Both models were well calibrated (AUC 0.79) and achieved external validation compared with international cohorts. CONCLUSIONS: Our study is the first to effectively validate both PCPTRC 2.0 and PBCG predictions for the Mexican population, proving that their use in daily practice improves biopsy decision making by accurately predicting HGPCa and limit unnecessary biopsies without representing additional costs to screening programs.


Assuntos
Biópsia/métodos , Tomada de Decisões/ética , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Saúde Pública/métodos , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450964

RESUMO

In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.


Assuntos
Metilação de DNA , Epigênese Genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Idoso , Ilhas de CpG , Reparo do DNA , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Porto Rico
5.
Prostate ; 80(4): 329-335, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868959

RESUMO

BACKGROUND: Several studies in the Caucasian population have shown that patients with Gleason 6 prostate cancer, based on surgical specimens, have low or no risk of metastasis. However, there is no data for men of African ancestry. The objective of this study was to estimate the overall, specific, and metastasis-free survival (MFS) of patients with a Gleason 6 score, based on the surgical specimen. PATIENTS AND METHODS: This was a monocentric retrospective study that included 723 consecutive patients treated by radical prostatectomy between 1 January 1 2000 and 31 March 2018, with a Gleason score of 6 based on the surgical specimen. Specific survival (SS) was defined as the time elapsed between surgery and death attributed to prostate cancer. Overall survival was defined as the time elapsed between surgery and death from all causes. The causes of death were verified in the medical records. Survival analyses without biochemical recurrence (BCR) and without salvage treatment were performed according to the Kaplan-Meier method. The Cox model was used for univariate and multivariate analyses. RESULTS: In total, 691 patients were included because 32 were excluded for missing data. Overall 5- and 10-year survival was 94.2% and 87.1%, respectively. SS and MFS were 100%, with a median follow-up of 8.5 years. The BCR rate was 16.5%, with a median time to BCR of 5.1 years. The frequency of salvage treatment was 13.0%, with a median time to surgery of 7.3 years. In univariate analysis, PSA, pathological stage, seminal vesicle invasion, positive margins, and lymph node dissection were significantly associated with an increased risk of BCR and salvage treatment, but only PSA and positive margins were significantly associated by multivariate analysis. DISCUSSION/CONCLUSION: No metastasis or disease-specific deaths were observed for men with Gleason score ≤6 prostate cancer at radical prostatectomy, in particular, men of African ancestry.


Assuntos
População Negra/estatística & dados numéricos , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/mortalidade , Idoso , Região do Caribe/etnologia , Estudos de Coortes , Guadalupe/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
6.
Mol Cell Endocrinol ; 502: 110659, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31816356

RESUMO

Prostate cancer (PCa) is one of the most prevalent male tumours. Stanniocalcin-1 (STC1) is a glycoprotein and, although the role of STC1 in human cancer is poorly understood, it is suggested to be involved in the development and progression of different neoplasms. This study investigated the protein expression profile of STC1 in PCa and benign prostatic hyperplasia (BPH) samples and STC1 signalling during cell proliferation and cell death in vitro using cell lines. We found higher levels of STC1 in PCa when compared to BPH tissue and that STC1 inhibited forskolin stimulation of cAMP in PC-3 cells. A monoclonal antibody against STC1 was effective in reducing cell proliferation, in promoting cell cycle arrest, and in increasing apoptosis in the same cells. Since STC1 acts as a regulator of prostatic tissue signalling, we suggest that this protein is a novel candidate biomarker for prostate tumour clinical progression and a potential therapeutic target.


Assuntos
Biomarcadores Tumorais/metabolismo , Colforsina/farmacologia , Glicoproteínas/genética , Glicoproteínas/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Masculino , Células PC-3 , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Regulação para Cima
7.
Proteomics ; 19(21-22): e1900174, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31576646

RESUMO

The histology-based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label-free LC-MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D-20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.


Assuntos
Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteoma/metabolismo , Progressão da Doença , Humanos , Masculino , Gradação de Tumores , Proteômica
8.
Prostate ; 79(14): 1640-1646, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376218

RESUMO

BACKGROUND: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort. METHODS: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression. RESULTS: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903). CONCLUSION: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa.


Assuntos
População Negra , Neoplasias da Próstata/patologia , Idoso , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Paris , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/química , Estudos Retrospectivos , Fatores de Risco , Regulador Transcricional ERG/análise , Índias Ocidentais , População Branca
9.
Int J Mol Sci ; 20(12)2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212728

RESUMO

The human protein Polybromo-1 (PBMR1/BAF180) is a component of the SWI/SNF chromatin-remodeling complex that has been reported to be deregulated in tumors. However, its role in prostate cancer (PCa) is largely unknown. In this study, we described the PBRM1 transcriptional levels and the protein expression/localization in tissues of PCa patients and in prostatic cell lines. Increased PBRM1 mRNA levels were found in PCa samples, when compared to benign disease, and were correlated with higher Gleason score. We also verified that only the nuclear localization of PBRM1 protein is correlated with a more aggressive disease and high Prostate-Specific Antigen (PSA) levels in tissue microarrays. Intriguing expression patterns of mRNA and protein were identified in the cell lines. Although PBRM1 protein was restricted to the nuclei, in tumor cell lines in non-neoplastic cells, it was also present in vesicular-like structures that were dispersed within the cytoplasm. We knocked-down PBRM1 in the castration-resistant PCa (CRPC) cell line PC-3 and we verified that PBRM1 promotes the expression of several markers of aggressiveness, including EpCAM, TGF-ß, and N-Cadherin. Therefore, our data supported the hypothesis that PBRM1 displays a pivotal role in the promotion and maintenance of the malignant behavior of PCa, especially in CRPC.


Assuntos
Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Proteínas de Ligação a DNA , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
10.
Res Vet Sci ; 122: 86-92, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30476726

RESUMO

The mTOR/4E-BP1/eIF4E pathway plays important roles in the neoplastic transformation process and in tumour growth. In men, the mTOR/4E-BP1/eIF4E pathway was described as altered in different tumours, including prostate cancer (PC). Apart from humans, the dog is the only species that develops PC with high frequency and is considered a good model for comparative oncology initiatives. Due to limited information on this pathway in canine tumours, this study aimed to investigate mTOR, 4E-BP1 and eIF4E gene and protein expression in canine PC, as well as in metastatic and normal prostatic tissues, and to evaluate the correlations between gene/protein expression and Gleason score (GS) in PC. A total of 35 formalin-fixed paraffin-embedded (FFPE) samples, including 13 of normal prostatic tissue, 17 PC samples and 5 metastasis samples, were evaluated by immunohistochemistry and qPCR. mTOR gene mutation in the kinase domain was also investigated. We identified higher p-mTOR and eIF4E protein levels in canine PC with higher GS values (≥ 8) and a significant positive correlation in expression between these proteins. eIF4E overexpression was observed in metastasis relative to expression in normal samples. Our data suggest that p-mTOR and eIF4E expression is positively correlated with GS in canine PC, similar to the pattern in humans. More studies of the mTOR/4EBP1/eIF4E pathway should be performed to identify possible correlations of the proteins involved with clinical and pathologic findings in canine PC and the roles of these proteins as therapeutic targets for the treatment of canine PC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Fosfoproteínas/metabolismo , Neoplasias da Próstata/veterinária , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Doenças do Cão/metabolismo , Cães , Fator de Iniciação 4E em Eucariotos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Fosfoproteínas/genética , Fosforilação , Neoplasias da Próstata/metabolismo , Serina-Treonina Quinases TOR/genética
11.
Appl. cancer res ; 39: 1-8, 2019. ilus, tab
Artigo em Inglês | LILACS, Inca | ID: biblio-994785

RESUMO

Background: Epidermal growth factor receptor (EGFR) is potential prognostic biomarker expressed in many human cancers. Prognostic significance of EGFR immunohistochemical expression has not been established in prostatic acinar adenocarcinoma, therefore we aimed to evaluate the frequency of expression of EGFR in prostatic adenocarcinoma and its association with other prognostic parameters. Methods: The study included 123 cases of biopsy proven prostatic acinar adenocarcinoma treated at Liaquat National hospital, Karachi from January 2013 till December 2017. Paraffin blocks of all cases were retrieved; sections were cut and stained with haematoxylin and eosin. Pathologic characteristics including tumor quantification, WHO grade group, gleason score, perineural and lymphovascular invasion were evaluated. EGFR immunohistochemistry (IHC) was performed on all tissue blocks. Results: Mean age of the patients included in the study was 69.05±8.68years. High gleason scores i.e. 8 & 9 were noted in 22% (27 cases) and 22.8% (28 cases) respectively. Similarly, 22.8% (28 cases) showed WHO grade group 5. 52.8% (65 cases) had > 50% tissue involvement by carcinoma and perineural invasion was seen in 37.4% (46 cases). Positive EGFR expression was noted in 18.7% (23 cases), while 81.3% (100 cases) showed negative EGFR expression. Significant association of EGFR expression was noted with gleason score (p-value = < 0.001), WHO grade (p = < 0.001), tumor quantification (p =0.007) and perineural invasion (p = < 0.001). Moreover, significant association of EGFR expression was also seen with disease recurrence and Her2neu over expression. Patients with low gleason scores (score 6 and 7) and lower grade group (1, 2 & 3) were less likely to have positive EGFR expression as compared to patients with high gleason score (score 9) and higher grade group (5). Similarly, patients with perineural invasion were more likely to have positive EGFR expression. Conclusion: We found a relatively low EGFR expression in our patients with prostatic adenocarcinoma; however, its association with poor prognostic parameters like high gleason score, higher grade group, perineural invasion, higher tissue involvement by cancer and disease recurrence signifies its importance as a prognostic parameter in prostatic acinar adenocarcinoma (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Próstata/patologia , Carcinoma de Células Acinares/patologia , Receptores ErbB/análise , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biomarcadores Tumorais , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/genética , Intervalo Livre de Doença , Gradação de Tumores
12.
Clin Med Insights Pathol ; 10: 1179555717740130, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29147082

RESUMO

BACKGROUND: The Gleason score is an essential tool in the decision to treat localized prostate cancer. However, experienced pathologists can classify Gleason score differently than do low-volume pathologists, and this may affect the treatment decision. This study sought to assess the impact of pathology review of external biopsy specimens from 23 men with a recent diagnosis of localized prostate cancer. METHODS: All external biopsy specimens were reviewed at our pathology department. Data were retrospectively collected from scanned charts. RESULTS: The median patient age was 63 years (range: 46-74 years). All patients had a Karnofsky performance score of 90% to 100%. The median prostate-specific antigen level was 23.6 ng/dL (range: 1.04-13.6 ng/dL). Among the 23 reviews, the Gleason score changed for 8 (35%) patients: 7 upgraded and 1 downgraded. The new Gleason score affected the treatment decision in 5 of 8 cases (62.5%). CONCLUSIONS: This study demonstrates the need for pathology review in patients with localized prostate cancer before treatment because Gleason score can change in more than one-third of patients and can affect treatment decision in almost two-thirds of recategorized patients.

13.
Acta biol. colomb ; 21(3): 533-542, set.-dic, 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-827631

RESUMO

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.

14.
Biosens Bioelectron ; 85: 171-177, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27176915

RESUMO

The research for new biomarkers of cancer has studied the role of fetuin glycoprotein on the metastatic disease diagnosis. Cratylia mollis is a lectin with high finity to fetuin, and used here to differentiate prostate cancer and benign prostatic hyperplasia. A label-free electrochemical nanosensor based on assembled carboxylated carbon nanotubes (COOH-CNTs) and poly-L-lysine (PLL) film was developed and applied to serum samples of prostate cancer positive for Gleason score. The electrode analytical response to fetuin in PBS samples, obtained by square wave voltammetry, exhibited a linear range from 0.5 to 25µgmL(-1), with a high correlation coefficient (r=0.994, p<0.001) and low limit of detection (0.017µgmL(-1)). The lectin nanoelectrode showed a good repeatability (1.24% RSD) and reproducibility (4.24% RSD). A pool of serum samples from prostate cancer patients with known the Gleason score were tested showing a significant statistically correlation. Thus, the lectin nanoelectrode was able to distinguish the degree of staging prostate cancer, providing the diagnostic differentiation of benign and malign hyperplasia. To the best of our knowledge, it is the first biosensor for this application using a lectin.


Assuntos
Técnicas Eletroquímicas/métodos , Fabaceae/química , Fetuínas/análise , Nanotubos de Carbono/química , Lectinas de Plantas/química , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Técnicas Biossensoriais/métodos , Diagnóstico Diferencial , Eletrodos , Humanos , Proteínas Imobilizadas/química , Limite de Detecção , Masculino , Polilisina/química , Próstata/patologia , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Reprodutibilidade dos Testes
15.
Rev. chil. urol ; 79(2): 56-60, 2014. tab, graf
Artigo em Espanhol | LILACS | ID: lil-785344

RESUMO

Evaluar pacientes con puntaje de Gleason de 7 sometidos a Prostatectomía Radical (PR) y determinar factores predictores de sobrevida libre de recidiva bioquímica (SL-RB). MATERIALES Y MÉTODOS: Se analizó una cohorte histórica de 1059 pacientes con Cáncer de Próstata sometidos a PR entre 1999 y 2012, de los cuales 490 cumplieron criterios de inclusión. Se definió como recidiva bioquímica (RB) un APE >0,2 ng/ml. Se consideró significativo un valor p < 0.05. RESULTADOS: La edad promedio y mediana de APE preoperatorio fue de 63 años y 6.6 ng/ml, respectivamente. Se observó RB en el 19,8 por ciento de esta serie con una mediana de seguimiento de 49 meses. El análisis multivariado demostró que los márgenes quirúrgicos (MQ) positivos (HR 1,76, p=0,01), T patológico (pT2 versus pT3, HR 2,0, p=0,007) y el porcentaje de cáncer en la pieza operatoria (HR 1,01, p=0,002) son predictores de SL-RB. El Gleason primario (3+4 versus 4+3) no fue un predictor de SL-RB (p=0,29). CONCLUSIONES: El Gleason primario no es un factor relevante para predecir RB en pacientes con GS 7 patológico. Sin embargo, los MQ positivos, el porcentaje de cáncer en la pieza operatoria, APE preoperatorio y la presencia pT3 son factores predictores de RB en pacientes con GS 7 y por lo tanto a considerar para decidir terapia adyuvante.


To evaluate patients with Gleason score 7 who underwent radical prostatectomy (RP) and to determine predictors of biochemical recurrence-free survival (SL-RB). MATERIALS AND METHODS: A historical cohort of 1059 patients with prostate cancer who underwent RP between 1999 and 2012, of which 490 met the inclusion criteria were analyzed. Biochemical recurrence (BR) was defined as a PSA > 0.2 ng / ml. A value of p < 0.05 was considered significant. RESULTS: Mean age was 63y-o and median preoperative PSA and 6.6 ng / ml. RB was observed in 19.8 percent of this series, with a median follow up of 49 months. Multivariate analysis showed that positive surgical margins (MQ) (HR 1.76, p = 0.01), pathological T (pT2 versus pT3, HR 2.0, p = 0.007) and the percentage of cancer in the surgical specimen (HR 1.01, p = 0.002) were predictors of SL-RB. Primary Gleason (3 +4 versus 4 +3) was not a predictor of SL-RB (p = 0.29). CONCLUSIONS: Primary Gleason is not relevant for predicting biochemical recurrence (RB) in patients with GS 7 pathological factor. However, positive margins, percentage of cancer in the surgical specimen, preoperative PSA and the presence pT3 are predictors of RB in patients with GS 7 and therefore they must be considered to decide for adjuvant therapy.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/cirurgia , Prostatectomia/métodos , Análise Multivariada , Estadiamento de Neoplasias , Seguimentos , Previsões , Recidiva , Recidiva Local de Neoplasia , Intervalo Livre de Doença
16.
Rev. chil. urol ; 78(4): 57-61, ago. 2013. tab, graf
Artigo em Espanhol | LILACS | ID: lil-774919

RESUMO

La vigilancia activa (VA) constituye una alternativa de manejo válida para pacientes con cáncer de próstata que cumplen con ciertos criterios que incluyen las características anatomopatológicas de la biopsia preoperatoria transrectal. La subgraduación del puntaje de Gleason en la biopsia preoperatoria respecto de la biopsia definitiva se reporta en un 24-39 por ciento de los casos, lo que constituye un problema al momento de querer incluir a un paciente en un protocolo de vigilancia. El objetivo principal de este estudio consistió en determinar el porcentaje de subgraduación del score de Gleason en biopsias preoperatorias de pacientes que cumplían criterios para VA pero que fueron sometidos a prostatectomía radical y la relación con el número de punciones realizadas y el porcentaje de subgraduación. Se incluyó restrospectivamente a 167 pacientes sometidos a prostatectomía radical, que por sus características preoperatorias cumplían criterios para ingresar a un protocolo de VA. Se evaluó la concordancia entre las biopsias preoperatorias y definitivas y además la relación entre el número de punciones realizadas y el nivel de subgraduación. 52 pacientes (31,1 por ciento) tuvieron un puntaje de Gleason mayor a 6 (GS 7 n=49; GS 8 n=3) en la biopsia definitiva. El menor porcentaje de subgraduación (23.4 por ciento) se observó en el grupo de pacientes que se sometió a biopsias preoperatorias que incluyeron 15 o más punciones. La biopsia prostática preoperatoria presenta un significativo porcentaje de subgraduación respecto a la biopsia definitiva, que tiende a disminuir al aumentar el número de punciones realizadas. Estos factores deben ser considerados al momento de ofrecer al paciente su ingreso a un protocolo de VA.


Active surveillance (AS) is a validated alternative for the management of patients with prostate cancer that meet certain criteria including the histopathological characteristics of preoperative transrectal biopsy. The down-grading of preoperative Gleason score compared to postoperative biopsy is reported in 24-39 percent of cases, which represents a significative problem to include a patient in a AS protocol. The main objective of this study was to determine the percentage of down-grading Gleason score compared to postoperative biopsy is reported in 24-39 percent of cases, which represents a significative problem to include a patient in a AS protocol. The main objective of this study was to determine the percentage of down-grading of the preoperative Gleason score compared to the definitive score in biopsy specimens from patients that met criteria for AS but that were subjected to a radical prostatectomy, and the relation between the number of punctures and the percentage of downgrading. 167 patients subjected to radical prostatectomy were retrospectively included, all of them having preoperative characteristics that fulfilled the criteria for entry into an AS protocol. We evaluated the correlation between preoperative and postoperative biopsies. We also evaluated the relationship between the number of punctures and the percentage of down-grading in the preoperative biopsy. RESULTS: 52 patients (31.1 percent) were found to have a Gleason score higher than 6 (GS 7 n=49; GS 8 n=3) in the definitive biopsy. The lowest percentage of downgrading (23.4 percent) was observed in the group of patients with preoperative biopsies that included 15 or more punctures. The preoperative prostatic biopsy has a significant percentage of downgrading compared to the definitive biopsy, which tends to decrease with increasing the number of punctures. These factors must be considered when offering AS to a patient.


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Biópsia/métodos , Conduta Expectante , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Prostatectomia , Reto
17.
Clinics ; Clinics;68(6): 820-824, jun. 2013. tab, graf
Artigo em Inglês | LILACS | ID: lil-676950

RESUMO

OBJECTIVE: To evaluate the concordance between the Gleason scores of prostate biopsies and radical prostatectomy specimens, thereby highlighting the importance of the prostate-specific antigen (PSA) level as a predictive factor of concordance. METHODS: We retrospectively analyzed 253 radical prostatectomy cases performed between 2006 and 2011. The patients were divided into 4 groups for the data analysis and dichotomized according to the preoperative PSA, <10 ng/mL and ≥10 ng/mL. A p-score <0.05 was considered significant. RESULTS: The average patient age was 63.3±7.8 years. The median PSA level was 9.3±4.9 ng/mL. The overall concordance between the Gleason scores was 52%. Patients presented preoperative PSA levels <10 ng/mL in 153 of 235 cases (65%) and ≥10 ng/mL in 82 of 235 cases (35%). The Gleason scores were identical in 86 of 153 cases (56%) in the <10 ng/mL group and 36 of 82 (44%) cases in the ≥10 ng/mL group (p = 0.017). The biopsy underestimated the Gleason score in 45 (30%) patients in the <10 ng/mL group and 38 (46%) patients in the ≥10 ng/mL (p = 0.243). Specifically, the patients with Gleason 3 + 3 scores according to the biopsies demonstrated global concordance in 56 of 110 cases (51%). In this group, the patients with preoperative PSA levels <10 ng/dL had higher concordance than those with preoperative PSA levels ≥10 ng/dL (61% x 23%, p = 0.023), which resulted in 77% upgrading after surgery in those patients with PSA levels ≥10 ng/dl. CONCLUSION: The Gleason scores of needle prostate biopsies and those of the surgical specimens were concordant in approximately half of the global sample. The preoperative PSA level was a strong predictor of discrepancy and might improve the identification of those patients who tended to be upgraded after surgery, particularly ...


Assuntos
Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/patologia , Biópsia por Agulha , Gradação de Tumores , Valor Preditivo dos Testes , Período Pré-Operatório , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Valores de Referência , Estudos Retrospectivos
18.
World J Oncol ; 4(2): 87-94, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29147337

RESUMO

BACKGROUND: The relationship between hyperglycemia and prostate cancer remains controversial. According to current hypotheses, elevated serum glucose levels may lead to disease development or disease prevention. Our study examined the potential correlation between pre-operative glycemic levels of patients with prostate cancer and the grade of tumor aggressiveness. METHOD: We studied the case files of patients with a diagnosis of prostate cancer who had received putatively curative cancer surgery at the Urology Department of the Servidores do Estado Federal Hospital (RJ/Brazil). We transcribed information related to glycemia - collected up to 3 months before the surgery - and the histopathological grade of tumor aggressiveness (Gleason score) of the surgically removed prostates. RESULTS: We analyzed 42 people who met the inclusion criteria. Based on Gleason scores, among the normoglycemic patients, we detected low, moderate, and highly aggressive neoplasias in 13%, 53%, and 36% of the cases, respectively. For the hyperglycemic group, these rates were 30%, 60%, and 10%, respectively. Normoglycemic patients had primary Gleason grade 3 in 40% of the cases and grade 4 in 60% of the cases. For the hyperglycemic patients, these rates were 90% and 10%, respectively (P < 0.05 vs. grade 3 group). CONCLUSION: Both Gleason score and primary Gleason grade were lower in hyperglycemic patients with prostate cancer than in normoglycemic patients, suggesting a "protective action" of hyperglycemic states.

19.
Int. braz. j. urol ; 38(6): 760-768, Nov-Dec/2012. tab, graf
Artigo em Inglês | LILACS | ID: lil-666022

RESUMO

Introduction

The widespread screening programs prompted a decrease in prostate cancer stage at diagnosis, and active surveillance is an option for patients who may harbor clinically insignificant prostate cancer (IPC). Pathologists include the possibility of an IPC in their reports based on the Gleason score and tumor volume. This study determined the accuracy of pathological data in the identification of IPC in radical prostatectomy (RP) specimens. Materials and Methods

Of 592 radical prostatectomy specimens examined in our laboratory from 2001 to 2010, 20 patients harbored IPC and exhibited biopsy findings suggestive of IPC. These biopsy features served as the criteria to define patients with potentially insignificant tumor in this population. The results of the prostate biopsies and surgical specimens of the 592 patients were compared. Results

The twenty patients who had IPC in both biopsy and RP were considered real positive cases. All patients were divided into groups based on their diagnoses following RP: true positives (n = 20), false positives (n = 149), true negatives (n = 421), false negatives (n = 2). The accuracy of the pathological data alone for the prediction of IPC was 91.4%, the sensitivity was 91% and the specificity was 74%. Conclusion

The identification of IPC using pathological data exclusively is accurate, and pathologists should suggest this in their reports to aid surgeons, urologists and radiotherapists to decide the best treatment for their patients. .


Assuntos
Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Biópsia , Carcinoma/cirurgia , Gradação de Tumores , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos Testes , Carga Tumoral
20.
Rev. Soc. Bras. Clín. Méd ; 10(5)set-out. 2012.
Artigo em Português | LILACS | ID: lil-652300

RESUMO

JUSTIFICATIVA E OBJETIVOS: O escore de Gleason da biópsia prostática transretal representa um dos métodos prognósticos mais importantes na avaliação dos cânceres de próstata, permitindo a indicação terapêutica mais adequada. O objetivo deste estudo foi comparar os valores do escore de Gleason obtidos na biópsia com os valores da peça cirúrgica a fim de obter valores a respeito do grau de concordância entre os dois métodos diagnósticos. MÉTODO: Foram estudados retrospectivamente os prontuários de 70 pacientes com diagnóstico anatomopatológico de adenocarcinoma prostático que foram submetidos à prostatectomia, atendidos em clínica de Oncologia na cidade de Salvador-BA, no período de 1998 a 2009. Os dados foram analisados pelo software SPSS 19.0. Foi utilizado o teste Kappa para avaliar a concordância entre os escores de Gleason da biópsia prostática transretal e aqueles da peça cirúrgica. RESULTADOS: A idade média dos pacientes foi 61,61 anos ± 7,25. O antígeno prostático específico (PSA) total pré-operatório teve média de 7,32 ng/mL ± 4,57. O escore de Gleason mais frequente foi 6, tendo 49 pacientes apresentado este valor à biópsia e 44 pacientes no espécime cirúrgico, 70% e 62,86%, respectivamente. Trinta e nove pacientes (55,71%) tinham Gleason 6(3+3) à biópsia e mantiveram o escore na peça cirúrgica. Houve concordância em 72,86% dos casos, subgradação em 21,43% e supergradação em 5,71%. O teste Kappa foi igual a +0,505 e o valor de p foi < 0,01. CONCLUSÃO: Ao comparar os resultados histológicos da biópsia prostática com os da peça cirúrgica, obteve-se concordância de 72,86%, com Kappa igual a +0,505; p < 0,01.


BACKGROUND AND OBJECTIVES: Gleason score of transrectal prostate biopsy is one of the most important prognostic methods in the evaluation of prostate cancers, allowing the most appropriate therapeutic indication. Our aim is to compare Gleason score values in biopsies with surgical specimens in order to obtain values about the degree of agreement between the two diagnostic methods. METHOD: We studied retrospectively 70 patients with anatomopathological diagnosis of prostatic adenocarcinoma who underwent prostatectomy in an Oncology clinic in the city of Salvador, in the state of Bahia, within 1998 to 2009. Data were analyzed by SPSS 19.0 software. Kappa was used to evaluate the agreement between Gleason scores of transrectal prostate biopsy and those of the surgical specimen. RESULTS: The average age of patients was 61.61 years ± 7.25. The preoperative prostatic specific antigen (PSA) had an average of 7.32 ng/mL ± 4.57. The most common Gleason score was 6. Forty-nine patients presented this score at the time of biopsy and 44 patients in surgical specimens (70% and 62.86% respectively). Thirty-nine patients (55.71%) had Gleason 6 (3+3) at the time of biopsy and the value remained the same in the surgical specimen. There was agreement in 72.86% of cases. We found underestimation in 21.43% and overestimation in 5.71%. Kappa was equal to +0.505 and the p value was < 0.01. CONCLUSION: When comparing the histological results of prostate biopsy with the surgical specimen we found agreement of 72.86%, with Kappa equal to +0,505, p < 0.01.


Assuntos
Humanos , Masculino , Idoso , Adenocarcinoma , Biópsia/métodos , Histologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Prostatectomia
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