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2.
Diagn Pathol ; 10: 189, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26470780

ABSTRACT

BACKGROUND: PD-L1 is a glycoprotein from the family of T-cell co-stimulatory molecules that are constitutively expressed by macrophages. Aberrant expression of PD-L1 is observed in human cancers associated with inhibition of the tumor-directed T-cell immune response. There are few reports in the literature evaluating PD-L1 expression in association to prognosis specifically in renal cell cancer clear cell type (RCC-CC). METHODS: Immunohistochemistry using a PD-L1 polyclonal antibody was performed on a tissue microarray (TMA) that contained 115 surgical specimens of RCC-CC. Cases were classified based on the absence or presence of staining intensity in the cytoplasm and membranes of the tumor cells. Statistical analysis was used to determine the association of PD-L1 expression with classic prognostic factors and tumor recurrence. RESULTS: PD-L1 expression was positive in 56.5 % of tumors. The univariate analysis showed a correlation between PD-L1 expression and nuclear Fuhrman grade (p = 0.021) and microvascular tumor embolization (p = 0.039). One hundred and four patients were monitored for a mean time of 115.7 months. Seventeen patients (16.3 %) suffered tumor recurrence. Negative outcomes were associated with higher nuclear grade tumors, PD-L1 expression, and the presence of microvascular invasion. CONCLUSION: Our findings confirm that PD-L1 expression is an important prognostic factor in RCC-CC.


Subject(s)
B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/chemistry , Kidney Neoplasms/chemistry , Aged , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Nephrectomy , Predictive Value of Tests , Retrospective Studies , Risk Factors , Time Factors , Tissue Array Analysis , Treatment Outcome
3.
Int Braz J Urol ; 40(2): 146-53, 2014.
Article in English | MEDLINE | ID: mdl-24856481

ABSTRACT

OBJECTIVE: Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy. MATERIALS AND METHODS: Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence. RESULTS: 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7. CONCLUSION: Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.


Subject(s)
Neoplasm Recurrence, Local/blood , Prostate-Specific Antigen/blood , Prostatectomy/methods , Prostatic Neoplasms/blood , Adult , Aged , Aged, 80 and over , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Predictive Value of Tests , Prostate/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Retrospective Studies , Risk Assessment , Risk Factors , Statistics, Nonparametric , Survival Analysis , Time Factors , Tumor Burden
4.
Int. braz. j. urol ; 40(2): 146-153, Mar-Apr/2014. tab, graf
Article in English | LILACS | ID: lil-711696

ABSTRACT

Objective Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy.Materials and Methods Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence.Results 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7.Conclusion Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.


Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Prostate-Specific Antigen/blood , Prostatectomy/methods , Prostatic Neoplasms/blood , Follow-Up Studies , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Predictive Value of Tests , Prostate/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Retrospective Studies , Risk Assessment , Risk Factors , Statistics, Nonparametric , Survival Analysis , Time Factors , Tumor Burden
6.
Int Braz J Urol ; 39(5): 649-56, 2013.
Article in English | MEDLINE | ID: mdl-24267108

ABSTRACT

PURPOSE: The discovery of new diagnostic tools for the diagnosis of prostate cancer (PCa) has become an important field of research. In this study, we analyzed the diagnostic value of the expression of the pepsinogen C (PGC) and prostate-specific membrane antigen (PSMA) genes in tissue samples obtained from prostate biopsies. MATERIALS AND METHODS: This study was comprised of 51 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies between January 2010 and March 2010. The biopsies were performed with 12 cores, and an additional core was randomly retrieved from the peripheral zone from each patient for study purposes. The expression of the PGC and PSMA genes was analyzed from the cDNA from the samples via the qRT-PCR technology. The expression patterns of patients with PCa were compared with those of patients without a PCa diagnosis. RESULTS: PSMA was overexpressed in only 43.4% of PCa cases, and PGC was overexpressed in 72.7% of cases. The median expression of PSMA was 1.5 times (0.1 to 43.9) and the median PGC expression was 8.7 times (0.1 to 50.0) the expression observed in prostatic tissue from TRUS-guided biopsies of normal patients. Analysis of patients with high-risk PCa indicated that PGC was overexpressed in 71.4% of cases (with a median expression of 10.6 times), and PSMA was overexpressed in only 35.7% of cases (with a median expression of 4.5 times). Among patients with low-risk PCa, PGC was also overexpressed in 71.4% of cases (with a median expression of 5.9 times), and PSMA was overexpressed in only 42.8% of cases (with a median expression of 2.5 times). CONCLUSIONS: PGC gene expression is significantly higher in prostatic tissue in men affected by PCa when compared to normal prostates. Further analyses are necessary to confirm our results.


Subject(s)
Antigens, Surface/analysis , Carcinoma/pathology , Glutamate Carboxypeptidase II/analysis , Pepsinogen C/analysis , Prostate/pathology , Prostatic Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antigens, Surface/genetics , Biopsy , Carcinoma/diagnostic imaging , Carcinoma/genetics , Gene Expression , Glutamate Carboxypeptidase II/genetics , Humans , Male , Middle Aged , Pepsinogen C/genetics , Prostate/diagnostic imaging , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/genetics , Real-Time Polymerase Chain Reaction , Reference Values , Risk Factors , Ultrasonography
7.
Int. braz. j. urol ; 39(5): 649-656, Sep-Oct/2013. tab, graf
Article in English | LILACS | ID: lil-695150

ABSTRACT

Purpose The discovery of new diagnostic tools for the diagnosis of prostate cancer (PCa) has become an important field of research. In this study, we analyzed the diagnostic value of the expression of the pepsinogen C (PGC) and prostate-specific membrane antigen (PSMA) genes in tissue samples obtained from prostate biopsies. Materials and Methods This study was comprised of 51 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies between January 2010 and March 2010. The biopsies were performed with 12 cores, and an additional core was randomly retrieved from the peripheral zone from each patient for study purposes. The expression of the PGC and PSMA genes was analyzed from the cDNA from the samples via the qRT-PCR technology. The expression patterns of patients with PCa were compared with those of patients without a PCa diagnosis. Results PSMA was overexpressed in only 43.4% of PCa cases, and PGC was overexpressed in 72.7% of cases. The median expression of PSMA was 1.5 times (0.1 to 43.9) and the median PGC expression was 8.7 times (0.1 to 50.0) the expression observed in prostatic tissue from TRUS-guided biopsies of normal patients. Analysis of patients with high-risk PCa indicated that PGC was overexpressed in 71.4% of cases (with a median expression of 10.6 times), and PSMA was overexpressed in only 35.7% of cases (with a median expression of 4.5 times). Among patients with low-risk PCa, PGC was also overexpressed in 71.4% of cases (with a median expression of 5.9 times), and PSMA was overexpressed in only 42.8% of cases (with a median expression of 2.5 times). Conclusions PGC gene expression is significantly higher in prostatic tissue in men affected by PCa when compared to normal prostates. Further analyses are necessary to confirm our results. .


Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Antigens, Surface/analysis , Carcinoma/pathology , Glutamate Carboxypeptidase II/analysis , Pepsinogen C/analysis , Prostate/pathology , Prostatic Neoplasms/pathology , Antigens, Surface/genetics , Biopsy , Carcinoma/genetics , Carcinoma , Gene Expression , Glutamate Carboxypeptidase II/genetics , Pepsinogen C/genetics , Prostate-Specific Antigen/blood , Prostate , Prostatic Neoplasms/genetics , Prostatic Neoplasms , Real-Time Polymerase Chain Reaction , Reference Values , Risk Factors
8.
Urol Oncol ; 31(6): 796-801, 2013 Aug.
Article in English | MEDLINE | ID: mdl-21880514

ABSTRACT

INTRODUCTION: Models of the multistep process related to cancer progression have been designed for many cancers including prostate. The aim of this study is to propose a new model including a possible role for recently described micro RNAs in prostate cancer (CaP) progression. METHODS: Sixty-three patients underwent radical prostatectomy to treat localized prostate carcinoma. The specimens of 15 patients were representative of high grade prostate intraepithelial neoplasia (HGPIN). Fourteen specimens represented localized favorable CaP, and 34 unfavorable, mostly non-organ-confined disease. Representing the advanced disease we studied 4 metastatic androgen-independent CaP and 2 cell lines. Micro RNAs were isolated using the mirVana miRNA Isolation kit and cDNA was obtained using the TaqMan miRNA Reverse Transcription kit to the miRNAs: hsa-miR-let7c, hsa-miR-15a, hsa-miR-16, hsa-miR-21, hsa-miR-25, hsa-miR-32, hsa-miR-100, hsa-miR-143, hsa-miR-145, hsa-miR-146a, hsa-miR-191, hsa-miR-199a, hsa-miR-206, and hsa-miR-218. Quantitative RT-PCR was carried out using the ABI 7500 Fast Real-Time PCR System and the TaqMan Universal PCR Master Mix. miRNA expression levels were measured by relative quantification, and fold expression changes were determined by the 2(-ΔΔCT) method. The small nucleolar RNA RNU43 was used as an endogenous control. RESULTS: Except for miR-21 and miR-206, the expression levels of all miRNAs significantly changed during the progression of CaP. Interestingly, there was a significant global loss of miRNA expression between HGPIN and metastasis at 2 important steps. The first was related to the transition from HGPIN to invasive adenocarcinoma, and the second was related to the transition from localized to metastatic adenocarcinomas. CONCLUSION: Through the analysis of 14 miRNAs in 4 groups of prostate lesions, which reproduced the progression of CaP, we showed that there is a global loss of miRNA expression at 2 distinct steps. The first related to the transition between HGPIN and localized invasive carcinoma, and the second associated with the transition from localized to metastatic CaP. The importance of our study is in the identification of possible miRNAs and miRNA-targeted genes involved in the progression of prostate carcinogenesis that may help the development of potential diagnostic or prognostic markers as well as the design of new target therapies.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , Prostatic Intraepithelial Neoplasia/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Adenocarcinoma/metabolism , Aged , Disease Progression , Humans , Male , Middle Aged , Neoplasm Metastasis , Prostate-Specific Antigen/blood , Real-Time Polymerase Chain Reaction , Treatment Outcome
9.
Urol Oncol ; 31(2): 175-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-21795075

ABSTRACT

OBJECTIVE: Perineural invasion (PNI) is detected in almost 20% of prostate biopsies and has been related to worse prognostic factors in radical prostatectomy (RP) specimens and lower disease-free survival rates. The aim of this study was to evaluate the importance of PNI during periods of extended prostate biopsies and to determine the value of this preoperative parameter as a predictor of pathologic findings in surgical specimens and in biochemical recurrence. MATERIALS AND METHODS: Between 2001 and 2009, 599 prostate biopsies and their respective RP specimens were examined in our laboratory. The RP specimens were always examined completely. The mean age of the patients was 61 years, and the mean PSA was 6.4 ng/mL. The mean and median number of biopsy cores obtained was 14.4 and 14, respectively. PNI was identified in 105 biopsies (17.5%). We studied the ability of PNI in prostate biopsies to determine the tumor stage in surgical specimens and the relationship of PNI with biochemical recurrence during a mean follow-up time of 51.4 months. RESULTS: The presence of PNI in prostate biopsies was observed in older patients (63 vs. 61 years old, P = 0.008). All of the prognostic factors determined for the RP specimens were significantly worse in patients with PNI compared with those without PNI. PNI was strongly associated with a higher pathologic stage (87% specificity, 40% sensitivity, odds ratio 4.8). Stage pT3 prostatic cancer was determined in 46 (43.8%) of 105 patients with PNI on biopsy compared to 69 (14%) of 494 patients without PNI (P = 0.01). Fifty-six (19.6%) patients had a biochemical recurrence, and PNI correlated significantly with PSA recurrence. A Kaplan-Meier analysis revealed a significant difference in recurrence-free survival between patients with and without PNI (45% vs. 53%, respectively, P = 0.021, log-rank test = 0.19). CONCLUSION: PNI is an important morphologic preoperative predictor of the pathologic stage as well as biochemical recurrence and must always be mentioned when adenocarcinoma is diagnosed on prostate biopsies.


Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/pathology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Biopsy , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms/surgery
10.
Int. braz. j. urol ; 38(6): 760-768, Nov-Dec/2012. tab, graf
Article in English | LILACS | ID: lil-666022

ABSTRACT

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. .


Subject(s)
Adult , Aged , Humans , Male , Middle Aged , Carcinoma/pathology , Prostate/pathology , Prostatic Neoplasms/pathology , Biopsy , Carcinoma/surgery , Neoplasm Grading , Predictive Value of Tests , Prostatectomy , Prostatic Neoplasms/surgery , Reproducibility of Results , Tumor Burden
11.
J Hered ; 103(3): 342-8, 2012.
Article in English | MEDLINE | ID: mdl-22315242

ABSTRACT

Cattle are divided into 2 groups referred to as taurine and indicine, both of which have been under strong artificial selection due to their importance for human nutrition. A side effect of this domestication includes a loss of genetic diversity within each specialized breed. Recently, the first taurine genome was sequenced and assembled, allowing for a better understanding of this ruminant species. However, genetic information from indicine breeds has been limited. Here, we present the first genome sequence of an indicine breed (Nellore) generated with 52X coverage by SOLiD sequencing platform. As expected, both genomes share high similarity at the nucleotide level for all autosomes and the X chromosome. Regarding the Y chromosome, the homology was considerably lower, most likely due to uncompleted assembly of the taurine Y chromosome. We were also able to cover 97% of the annotated taurine protein-coding genes.


Subject(s)
Cattle/genetics , Genome , Animals , Chromosomes, Mammalian/genetics , Codon/genetics , Contig Mapping , Male , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid
12.
Urol Oncol ; 30(1): 16-20, 2012.
Article in English | MEDLINE | ID: mdl-19945309

ABSTRACT

OBJECTIVE: By reason of its heterogeneous behavior, it is difficult to determine the prognosis of many prostate cancer cases. Patients with the same clinicopathologic conditions may present varying clinical findings and rates of progression. We determined the role of new genes as potential molecular markers for prostate cancer prognosis. MATERIALS AND METHODS: We performed a microarray analysis of two pools of patients with prostate cancer divided according to their clinicopathologic characteristics. After that, we validated these results by testing the genes with most different expressions between the two pools using the quantitative real time polymerase chain reaction method. We analyzed gene expression in 33 patients with localized prostate cancer according to prostate specific antigen (PSA), pathologic stage, Gleason score, and biochemical recurrence. For statistical analysis we used the Mann-Whitney Test. RESULTS: The microarray analysis revealed that 4,147 genes presented a different expression between the two pools. Among them, 3 genes, TMEFF2, GREB1, and TH1L, were at least 13-times overexpressed, and 1 gene, IGH3, which was at least 5 times under-expressed in pool 1 (good prognosis) compared with pool 2 (bad prognosis), were selected for analysis. After the validation tests, GREB1 was significantly more overexpressed among patients with stage T2 compared with T3 (P = 0.020). The expressions of other 3 genes did not present significant differences according to the clinicopathological variables. CONCLUSIONS: Tissue expression of GREB1 is associated with organ-confined prostate cancer and may constitute a gene associated with a favorable prognosis.


Subject(s)
Biomarkers, Tumor/genetics , Neoplasm Proteins/biosynthesis , Prostatic Neoplasms/genetics , Aged , Biomarkers, Tumor/analysis , Gene Expression Profiling , Humans , Male , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , Prognosis , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Reverse Transcriptase Polymerase Chain Reaction
13.
Int Braz J Urol ; 38(6): 760-8, 2012.
Article in English | MEDLINE | ID: mdl-23302398

ABSTRACT

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.


Subject(s)
Carcinoma/pathology , Prostate/pathology , Prostatic Neoplasms/pathology , Adult , Aged , Biopsy , Carcinoma/surgery , Humans , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Prostatectomy , Prostatic Neoplasms/surgery , Reproducibility of Results , Tumor Burden
14.
Urol Oncol ; 30(6): 794-7, 2012.
Article in English | MEDLINE | ID: mdl-21458310

ABSTRACT

INTRODUCTION AND OBJECTIVE: Because of the improvements on detection of early stage prostate cancer over the last decade, focal therapy for localized prostate cancer (PC) has been proposed for patients with low-risk disease. Such treatment would allow the control of cancer, thereby diminishing side effects, such as urinary incontinence and sexual dysfunction, which have an enormous impact on quality of life. The critical issue is whether it is possible to preoperatively predict clinically significant unifocal or unilateral prostate cancer with sufficient accuracy. Our aim is to determine whether there is any preoperative feature that can help select the ideal patient for focal therapy. MATERIAL AND METHODS: A total of 599 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy followed by radical prostatectomy to treat PC were examined in our laboratory between 2001 and 2009. We established very restricted criteria to select patients with very-low-risk disease for whom focal therapy would be suitable (only 1 biopsy core positive, tumor no larger than 80% of a single core, no perineural invasion, PSA serum level < 10 ng/ml, Gleason score < 7 and clinical stage T1c, T2a-b). We defined 2 groups of patients who would be either adequately treated or not treated by focal therapy. The primary endpoint was the evaluation of preoperative features in order to identify which parameters should be considered when choosing good candidates for focal therapy. RESULTS: Fifty-six out of 599 patients met our criteria. The mean age was 59 years, and the mean number of biopsy cores was 14.4. Forty-seven (83.9%) were staged T1c, and 9 (16.1%) were staged T2a-b. Forty-four (78.6%) patients could be considered to have been adequately treated by focal therapy, and 12 (21.4%) could not. There was no statistical difference between the 2 groups considering age, clinical stage, PSA levels, Gleason score, and tumor volume in the biopsy. All 12 patients who could be considered inadequately treated had a bilateral, significant secondary tumor, 58.3% had Gleason ≥ 7, and 25% were staged pT3. CONCLUSION: Although focal therapy might be a good option for patients with localized prostate cancer, we are so far unable to select which of them would benefit from it based on preoperative data, even using very restricted criteria, and a considerable proportion of men would still be left undertreated.


Subject(s)
Adenocarcinoma , Prostatic Neoplasms , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Risk Factors
15.
J Urol ; 185(3): 1118-22, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21255804

ABSTRACT

PURPOSE: Abnormal miRNA expression has emerged as crucial factors in carcinogenesis and is important in the comprehension of prostate cancer behavior. We determined the correlation of miRNA expression profiles with prostate cancer progression. MATERIALS AND METHODS: We studied frozen specimens from 49 patients treated for prostate cancer with radical prostatectomy. We intentionally chose 28 men without and 21 with biochemical recurrence, defined as prostate specific antigen greater than 0.2 ng/ml. The expression of 14 miRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction. All radical prostatectomy specimens were studied in toto to determine tumor volume, Gleason score and 2002 TNM pathological stage. Benign prostate tissue from benign prostatic hyperplasia served as a control. RESULTS: Four miRNAs were related to tumor recurrence. Using the Cox regression test the risk of recurrence was 3.0, 3.3, 2.7 and 3.4 for high levels of miR-100, miR-145, miR-191 and miR-let7c, respectively. When considering statistically significant clinical variables on univariate analysis of biochemical-free survival, prostate specific antigen and tumor volume, results revealed that miR-100 and tumor volume were independently related to tumor recurrence. CONCLUSIONS: A high level of miR-100 is related to biochemical recurrence of localized prostate cancer in patients treated with radical prostatectomy. The role of miR-100 during carcinogenesis must be resolved in future studies to better understand the molecular pathways in which miR-100 is involved. This may open the possibility of using it as a prognostic marker and inspire the development of a target drug.


Subject(s)
MicroRNAs/genetics , Prostatic Neoplasms/genetics , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/genetics , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology
16.
Urol Oncol ; 29(3): 265-9, 2011.
Article in English | MEDLINE | ID: mdl-19372056

ABSTRACT

OBJECTIVE: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. MATERIAL AND METHODS: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. RESULTS: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P<0.001), (55.550 vs. 8.314, P=0.010), and (33.549 vs. 2.748, P=0.001), respectively. CONCLUSION: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 ß3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies.


Subject(s)
Biomarkers, Tumor/genetics , Bone Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Aged , Bone Neoplasms/secondary , Follow-Up Studies , Gene Expression Profiling , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Prostatic Neoplasms/pathology
17.
Int Braz J Urol ; 36(5): 583-90, 2010.
Article in English | MEDLINE | ID: mdl-21044375

ABSTRACT

PURPOSE: Atypical glands (ASAP) are diagnosed in 5.0% of prostate biopsies, and cancer identification in a rebiopsy is higher than 40.0%. The use of antibodies to mark basal cells is currently a common practice, in order to avoid rebiopsies. There has been no reported study that has reviewed characteristics of radical prostatectomies (RPs) when immunohistochemistry (IHC) was necessary for definitive diagnosis. MATERIALS AND METHODS: Out of 4127 biopsies examined from 2004 to 2008, 144 (3.5%) were diagnosed with ASAP. IHC was performed using antibody anti-34ΒE12 and p63. The results of surgical specimens of 27 patients treated by RP after the diagnosis of prostate cancer (PC) was made using IHC (Group 1) were compared with 1040 patients where IHC was not necessary (Group 2). RESULTS: IHC helped to diagnose PC in 103 patients (71.5%). Twenty-seven (26.2%) underwent RP. In Group 1, two (7.4%) adenocarcinomas were insignificant versus 29 (2.9%) for Group 2. Patients from Group 1 were younger (p = 0.039), had lower Gleason scores (GS) (p < 0.001), lower percentage of Gleason pattern 4 (p < 0.001), and smaller tumors (p < 0.001). CONCLUSION: The use of IHC did not lead to diagnosis of insignificant tumors as illustrated by absence of differences in pathological stage or positive surgical margins in men submitted to RP. Therefore, our results suggest that this modality should be routinely used for a borderline biopsy and ASAP cases.


Subject(s)
Adenocarcinoma/pathology , Prostate/pathology , Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Biopsy , Cell Proliferation , Humans , Immunohistochemistry/methods , Male , Middle Aged
18.
Int. braz. j. urol ; 36(5): 583-590, Sept.-Oct. 2010. ilus, tab
Article in English | LILACS | ID: lil-567898

ABSTRACT

PURPOSE: Atypical glands (ASAP) are diagnosed in 5.0 percent of prostate biopsies, and cancer identification in a rebiopsy is higher than 40.0 percent. The use of antibodies to mark basal cells is currently a common practice, in order to avoid rebiopsies. There has been no reported study that has reviewed characteristics of radical prostatectomies (RPs) when immunohistochemistry (IHC) was necessary for definitive diagnosis. MATERIALS AND METHODS: Out of 4127 biopsies examined from 2004 to 2008, 144 (3.5 percent) were diagnosed with ASAP. IHC was performed using antibody anti-34ßE12 and p63. The results of surgical specimens of 27 patients treated by RP after the diagnosis of prostate cancer (PC) was made using IHC (Group 1) were compared with 1040 patients where IHC was not necessary (Group 2). RESULTS: IHC helped to diagnose PC in 103 patients (71.5 percent). Twenty-seven (26.2 percent) underwent RP. In Group 1, two (7.4 percent) adenocarcinomas were insignificant versus 29 (2.9 percent) for Group 2. Patients from Group 1 were younger (p = 0.039), had lower Gleason scores (GS) (p < 0.001), lower percentage of Gleason pattern 4 (p < 0.001), and smaller tumors (p < 0.001). CONCLUSION: The use of IHC did not lead to diagnosis of insignificant tumors as illustrated by absence of differences in pathological stage or positive surgical margins in men submitted to RP. Therefore, our results suggest that this modality should be routinely used for a borderline biopsy and ASAP cases.


Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Adenocarcinoma/pathology , Prostate/pathology , Prostatic Neoplasms/pathology , Biopsy , Cell Proliferation , Immunohistochemistry/methods
19.
Int J Radiat Oncol Biol Phys ; 73(2): 353-6, 2009 Feb 01.
Article in English | MEDLINE | ID: mdl-18774658

ABSTRACT

PURPOSE: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. METHODS AND MATERIALS: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. RESULTS: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. In 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. CONCLUSION: In the extended biopsy era and after the International Society of Urological Pathology consensus on GS, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects.


Subject(s)
Prostate/pathology , Prostatic Neoplasms/pathology , Adult , Aged , Biopsy, Needle , Chi-Square Distribution , Humans , Male , Middle Aged , Prostate/surgery , Prostatectomy , Prostatic Neoplasms/surgery , Regression Analysis , Retrospective Studies , Statistics, Nonparametric , Tumor Burden
20.
J Urol ; 181(2): 594-600, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19084862

ABSTRACT

PURPOSE: The diagnosis of prostate cancer in men with persistently increased prostate specific antigen after a negative prostate biopsy has become a great challenge for urologists and pathologists. We analyzed the diagnostic value of 6 genes in the tissue of patients with prostate cancer. MATERIALS AND METHODS: The study was comprised of 50 patients with localized disease who underwent radical prostatectomy. Gene selection was based on a previous microarray analysis. Among 4,147 genes with different expressions between 2 pools of patients 6 genes (PSMA, TMEFF2, GREB1, TH1L, IgH3 and PGC) were selected. These genes were tested for diagnostic value using the quantitative reverse transcription polymerase chain reaction method. Initially malignant tissue samples from 33 patients were analyzed and in the second part of the study we analyzed benign tissue samples from the other 17 patients with prostate cancer. The control group was comprised of tissue samples of patients with benign prostatic hyperplasia. RESULTS: Analysis of malignant prostatic tissue demonstrated that prostate specific membrane antigen was over expressed (mean 9 times) and pepsinogen C was under expressed (mean 1.3 x 10(-4) times) in all cases compared to benign prostatic hyperplasia. The other 4 tested genes showed a variable expression pattern not allowing for differentiation between benign and malignant cases. When we tested these results in the benign prostate tissues from patients with cancer, pepsinogen C maintained the expression pattern. In terms of prostate specific membrane antigen, despite over expression in most cases (mean 12 times), 2 cases (12%) presented with under expression. CONCLUSIONS: Pepsinogen C tissue expression may constitute a powerful adjunctive method to prostate biopsy in the diagnosis of prostate cancer cases.


Subject(s)
Biomarkers, Tumor/genetics , Pepsinogen C/metabolism , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Aged , Biopsy, Needle , Case-Control Studies , Diagnosis, Differential , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , Pepsinogen C/genetics , Probability , Prostate-Specific Antigen/genetics , Prostatectomy/methods , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/surgery , Prostatic Neoplasms/surgery , RNA, Neoplasm/analysis , Reverse Transcriptase Polymerase Chain Reaction , Risk Assessment , Sensitivity and Specificity , Statistics, Nonparametric , Ultrasound, High-Intensity Focused, Transrectal
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