Two livebirths achieved in cases of hypergonadotropic hypogonadism nonobstructive azoospermia, treated with GnRH agonist and gonadotrophins: a case series and review of the literature.

Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we report cases of two patients with NOA due to maturation arrest and increased serum FSH, treated with GnRH agonist and gonadotrophins. The two NOA patients underwent a pharmacological treatment consisting of pituitary desensibilization using a GnRH agonist and testicular stimulation using menotropin. Testicular stimulation started one month after the beginning of GnRH agonist treatment. The female partner underwent controlled ovarian stimulation (COS) followed by intracytoplasmic sperm injection (ICSI). On the third day of the cycle, menotropin daily doses was administered. When at least one follicle ≥14 mm was visualized, pituitary blockage was performed using GnRH antagonist ganirelix. When three or more follicles attained a mean diameter of ≥17 mm, triptorelin acetate was administered to trigger final follicular maturation. Oocyte retrieval was performed 35 hours later. After treatment, male partner blood levels of the FSH, LH, decreased and total testosterone were increased. Spermatozoa was observed after semen collection in both cases. After COS, oocytes were retrieved and ICSI was performed. Embryos were biopsied for preimplantation genetic testing (PGT) and those considered euploidy were transferred resulting in positive implantation, ongoing pregnancy, and livebirth on both cases. In this report we present a successful strategy for hypergonadotropic hypogonadism AOA men, as an alternative approach to the surgical testicular sperm recovery. Nevertheless, prospective randomized trials are needed to confirm our findings.

Validation of the Brazilian Version of Functional Assessment of Cancer Therapy-Prostate-FACT-P (Version 4) in Prostate Cancer Patients.

The purpose of this study is to validate the Brazilian version of Functional Assessment of Cancer Therapy-Prostate FACT-P (version 4) in nonmetastatic prostate cancer (PC) patients. Patients with histopathological diagnosis of PC were submitted to health-related quality of life (HRQOL) questionnaires - SF-36 (Medical Outcomes Study 36 - Item Short-Form Health Survey) and FACT-P (version 4). After 7 to 15 days, FACT-P (version 4) was reapplied in the sample's percentage that participated the first evaluation. Cronbach alpha coefficient was used to determine internal consistency and intraclass correlation coefficient (ICC) certified stability. Correlations between FACT-P (version 4) and SF-36 tested convergent validity. Regarding known groups validity, the hypothesis tested was that FACT-P (version 4) is capable of discriminating HRQOL in patients with different PC risk classifications. A total of 112 patients with nonmetastatic PC were evaluated. Cronbach alpha coefficients (0.64-0.88) and ICC (0.75-0.93) obtained satisfactory results of reliability. Verified correlations (r 0.3-0.72) between FACT-P (version 4) and SF-36 suggest convergent validity. In the studied sample, FACT-P (version 4) was unable to discriminate HRQOL in nonmetastatic patients. The Brazilian version of FACT-P questionnaire (version 4) showed evidences of reliability and validity on evaluating HRQOL in Brazilian men with nonmetastatic PC.

Sperm Selection for micro TESE-ICSI in Non-Obstructive Azoospermia, a Case Report.

TESE-ICSI (testicular sperm extraction associated with intracytoplasmic sperm injection) represents a technique to attain pregnancy in couples with non-obstructive azoospermia (NOA) and other unlikely situations. Because of the poor pregnancy outcomes obtained by this procedure, we need new sperm selection techniques to improve the livebirth rate of NOA patients. Here we describe a successful micro TESE-ICSI cycle performed with sperm selected through high magnification and polarized light microscopy in a couple with two previous ICSI failures.

Prognostic significance of architectural subtypes of Gleason grade 4 prostate cancer in radical prostatectomy: A semiquantitative method of evaluation.

Studies have shown that Gleason grade 4 extent as well as architectural subtypes provide prognostic information. We aimed to evaluate the influence on biochemical recurrence following radical prostatectomy of patients with organ-confined tumor, Gleason score 7, and negative surgical margins. Total tumor extent, Gleason grade 4 total extent and the extent of each architectural subtype (fused glands, poorly defined glands, cribriform glands, and glomeruloid glands) were evaluated by a semiquantitative point-count method using different colors to identify each subtype. Microscopic morphology of glomeruloid glands was considered regardless of morphology: size (small or large), attachment (narrow or extensive), and cribriform or solid intraluminal protrusion. Gleason grade 4 total extent significantly predicted shorter time to biochemical recurrence in univariate and multivariate analysis. Stratifying extent, Gleason grade 4 with >30% of the total grade 4 extent was significantly predictive for time of recurrence. Considering architectural subtypes, cribriform and glomeruloid glands but not fused and poorly formed glands extent, significantly predicted shorter time to recurrence in univariate analysis. An important issue related to the studies on prognostic significance of Gleason grade 4 subtypes is the lack of uniformity in the definition of microscopic morphology of the subtypes particularly of the glomeruloid architecture.

PSMA whole-body tumor burden in primary staging and biochemical recurrence of prostate cancer.

PURPOSE: The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. METHODS: We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed. RESULTS: Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p = < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV. CONCLUSION: PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.

Advanced renal cell carcinoma (RCC) management: an expert panel recommendation from the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG).

PURPOSE: The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients. METHODS: Eighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts. The voting panel comprised 26 specialists from the LACOG-GU/LARCG. Consensus was determined as 75% agreement. For questions with less than 75% agreement, a new discussion was held, and consensus was determined by the majority of votes after the second voting session. RESULTS: The recommendations were based on the highest level of scientific evidence or by the opinion of the RCC experts when no relevant research data were available. CONCLUSION: This manuscript provides guidance for advanced RCC treatment according to the LACOG-GU/LARCG expert recommendations.

Quality of life and sexual health in men with prostate cancer undergoing radical prostatectomy.

The aim of this study was to evaluate the relationship between quality of life, erectile function and group psychotherapy in patients with prostate cancer undergoing radical prostatectomy. Sixty patients were evaluated for erectile function (IIEF-5), quality of life (SF-36SF), urinary incontinence (ICQI-SF and ICQI-OAB). Thirty of them had group psychotherapy two weeks before and 12 weeks after surgery. Patients who underwent group psychotherapy had better scores in IIEF-5, satisfaction with life in general, satisfaction with sexual life and in partner relationship; better results of SF-36SF, excepting two domains: bodily pain and role emotional. There were significant correlations between IIEF-5 and perception of discomfort (p = .030), physical functioning (p = .021), physical component (p = .005) and role emotional (p = .009) in patients undergoing group psychotherapy. In patients who didn't have group psychotherapy there were significant correlations between ICQI-OAB and perception of discomfort (p = .025), social functioning (p = .052) and role emotional (p = .034); between ICQI-SF and perception of discomfort (p = .0001). Group psychotherapy has a positive impact in quality of life and erectile function. There was no difference in the urinary function of the two groups. Further studies are necessary to identify the impact of self-perception and self-knowledge in the postoperative management of radical prostatectomy.

Renal cell cancer treatment: an expert panel recommendation from the Latin American cooperative group-genitourinary and the Latin American renal cancer group: focus on surgery.

BACKGROUND: Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline. METHODS: Issues (134) related to the treatment of RCC were previously formulated by a panel of experts. The voting panel comprised 26 specialists (urologists and medical oncologists) from the LACOG-GU/LARCG. A consensus was reached if 75% agreement was achieved. If there was less concordance, a new discussion was undertaken, and a consensus was determined by the most votes after a second voting session. RESULTS: The expert meeting provided recommendations that were in line with the global literature; 75.0% of the recommendations made by the panel of experts were evidence-based level A, 22.5% of the recommendations were level B, and 2.5% of the recommendations were level D. CONCLUSIONS: This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer

ABSTRACT Purpose: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. Materials and Methods: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. Results: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. Conclusions: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer.

PURPOSE: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. MATERIALS AND METHODS: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. RESULTS: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. CONCLUSIONS: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

The importance of histopathologic review of biopsies in patients with prostate cancer referred to a tertiary uro - oncology center

ABSTRACT Introduction: In view of the detailed histologic evaluation of prostate cancer (PC), it is usually advisable to provide a "second opinion" to confirm diagnosis. This study aimed to compare the Gleason score (GS) of initial diagnosis versus that of histopathologic review of patients with PC. The secondary objective was to compare initial GS versus histopathologic review versus post - surgical histopathology. Material and methods: Retrospective study based on chart review of patients with PC that attended the Uro - oncology Department of Hospital das Clínicas - UNICAMP - Campinas, Brazil, from April, 2002, to April, 2012. Data were divided in groups: patients with biopsies performed elsewhere, biopsies after pathological review and histopathological results following retropubic radical prostatectomy (RRP). These were evaluated in relation to GS difference using Fleis's Kappa concordance coefficient. Results: 402 PC patients, with a median age of 66 years, were evaluated. Reviewed GS showed worsening, with accuracy of 61.2%, and Kappa concordance value = 0.466. Among 143 patients submitted to surgery, GS varied widely, regarding initial evaluation, review and post - surgical RRP. Joint concordance of evaluations was weak (Kappa = 0.216), mainly due to almost no existence concordance between initial evaluation and following RRP (Kappa = 0.041). Conclusion: There is a great histopathological variation of initial GS versus reviewed GS. There is also a better correlation of reviewed GS and post - surgical GS than with initial GS. The second opinion by an uropathologist improves diagnosis and should be advised for better therapeutic decision.

The importance of histopathologic review of biopsies in patients with prostate cancer referred to a tertiary uro-oncology center.

INTRODUCTION: In view of the detailed histologic evaluation of prostate cancer (PC), it is usually advisable to provide a "second opinion" to confirm diagnosis. This study aimed to compare the Gleason score (GS) of initial diagnosis versus that of histopathologic review of patients with PC. The secondary objective was to compare initial GS versus histopathologic review versus post - surgical histopathology. MATERIAL AND METHODS: Retrospective study based on chart review of patients with PC that attended the Uro - oncology Department of Hospital das Clínicas - UNICAMP - Campinas, Brazil, from April, 2002, to April, 2012. Data were divided in groups: patients with biopsies performed elsewhere, biopsies after pathological review and histopathological results following retropubic radical prostatectomy (RRP). These were evaluated in relation to GS difference using Fleis's Kappa concordance coefficient. RESULTS: 402 PC patients, with a median age of 66 years, were evaluated. Reviewed GS showed worsening, with accuracy of 61.2%, and Kappa concordance value = 0.466. Among 143 patients submitted to surgery, GS varied widely, regarding initial evaluation, review and post - surgical RRP. Joint concordance of evaluations was weak (Kappa = 0.216), mainly due to almost no existence concordance between initial evaluation and following RRP (Kappa = 0.041). CONCLUSION: There is a great histopathological variation of initial GS versus reviewed GS. There is also a better correlation of reviewed GS and post - surgical GS than with initial GS. The second opinion by an uropathologist improves diagnosis and should be advised for better therapeutic decision.

Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial.

Several biosimilar versions of enoxaparin are already approved and in use globally. Analytical characterization can establish good quality control in manufacturing, but they may not assure similarity in clinical outcomes between biosimilar and branded enoxaparin. This study evaluated the efficacy and safety of biosimilar Cristália versus branded Sanofi enoxaparin in venous thromboembolism (VTE) prevention in patients undergoing major abdominal surgery at risk for VTE. In this randomized, prospective single-blind study, we compared Cristália enoxaparin (Ce), a biosimilar version, versus branded Sanofi enoxaparin (Se; at a dose of 40 mg subcutaneously per day postoperatively from 7 to 10 days) in 243 patients submitted to major abdominal surgery at risk for VTE for VTE prevention. The primary efficacy outcome was occurrence of VTE or death related to VTE. The principal safety outcomes were a combination of major bleeding and clinically relevant non-major bleeding. Bilateral duplex scanning of the legs was performed from days 10 to 14, and follow-ups were performed up to 60 days after surgery. The incidence of VTE was 4.9% in the Cristália group and 1.1% in the Sanofi group (absolute risk difference = 3.80%, 95% confidence interval [CI]: -1.4%-9.0%) yielding noninferiority since the 95% CI does not reach the prespecified value Δ = 20%. Clinically significant bleeding occurred in 9.9% in the Cristália group and in 5.5% in the Sanofi group (n.s. ). In conclusion, this study suggests that 40 mg once daily of Ce, a biosimilar enoxaparin, is as effective and safe as the branded Sanofi enoxaparin in the prophylaxis of VTE in patients submitted to major abdominal surgery at risk for VTE.

Capillary zone electrophoresis method to assay tipranavir capsules and identification of oxidation product and organic impurity by quadrupole-time of flight mass spectrometry.

Tipranavir (TPV) is one of the most recently developed protease inhibitors (PI) and it is specially recommended for treatment-experienced patients who are resistant to other PI drugs. In this work, a simple and friendly environmental CZE stability-indicating method to assay TPV capsules was developed and two TPV organic impurities were identified by high resolution mass spectrometry (HRMS). The optimized analytical conditions were: background electrolyte composed of sodium borate 50mM, pH 9.0 and 5% of methanol; voltage + 28kV; hydrodynamic injection of 5s (100mbar), detection wavelength 240nm, at 25°C. The separation was achieved in a fused silica capillary with 50µm × 40cm (inner diameter × effective length), using furosemide as internal standard. All the validation parameters were met and the method was specific, even in the presence of degradation products and impurities. Oxidation was indicated as the main degradation pathway among those evaluated in this study (acidic, alkaline, thermal, photolytic and oxidative) and it showed a second order degradation kinetic, under the conditions used in this study. The main oxidation product and an organic impurity detected in the standard were characterized by Q-TOF, and both of them correspond to oxidation products of TPV.

Steroid Hormone Receptors as Potential Mediators of the Clinical Effects of Dutasteride: A Prospective, Randomized, Double-Blind Study.

This study characterizes the clinical and morphofunctional effects of a 5α-reductase inhibitor on steroid hormone receptors in normal human prostate tissue, as potential mediators of the clinical effects of dutasteride. This work was a prospective, double-blind, and randomized study that evaluated 49 men aged between 45 and 70 years, with no alterations in a digital rectal examination and prostate-specific antigen measurements between 2.5 and 4.0 ng/mL. These patients underwent prostate biopsy guided by transretal ultrasound with prostate neoplasia being ruled out, and the patients were divided into two groups, with one group receiving dutasteride ( n = 25) and one group receiving a placebo ( n = 24). The patients were clinically assessed each quarter, and at the end of 12 months they underwent new laboratory tests, prostate rebiopsy, and histopathological, immunohistochemical and clinical analyses. The estrogen receptor-beta (ERß) and androgen receptor immunoreactivities were higher, and the proliferation/apoptotic ratio was significantly lower with predominance of the apoptotic process, followed by a significant reduction in the prostate volume and the total serum prostate-specific antigen levels in the dutasteride group when compared with the placebo group, with a clear supremacy of ERß. There were no significant variations in the serum estrogen and testosterone levels, in the body mass index, or in the ERα immunoreactivities in the dutasteride and placebo groups. The results demonstrated the importance of the ERß pathway in the activation mechanisms of apoptosis, exerting a protective effect in the normal prostate, indicating that this receptor might be an important mediator of the clinical effects of dutasteride.

Lipocalina associada à gelatinase neutrofílica(NGAL) como um biomarcador de lesão renal: uma revisão / Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney damage: a review

Lipocalina associada à gelatinase neutrofílica (NGAL) é uma molécula proteica predominantemente expressa na parte distal do néfron após a ocorrência de lesão renal. Diferentemente da creatinina sérica e da taxa de filtração glomerular, que são marcadores de função renal, os níveis aumentados de NGAL, tanto no soro quanto na urina, estão intimamente ligados a lesões estruturais do néfron.Os estudos clínicos indicam que poucas horas após a ocorrência da lesão renal aguda os níveis séricos e urinários de NGAL já se apresentam significativamente elevados, enquanto os níveis séricos de creatinina e a sua depuração renal apenas sofrem alterações significativas entre 24-48hapós a lesão. Assim, a utilização de marcadores de função renal, usualmente avaliados na práticaclínica, pode apresentar algumas limitações além de dificultar a aplicação de medidas precoces quevisam a proteção renal. Esta revisão da literatura tem por objetivo analisar os aspectos biológicos e as aplicações da mensuração de NGAL em algumas condições clínicas, incluindo injúria renal, nefropatias e isquemia renal.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein molecule predominantly expressed in the distal part of the nephron following the occurrence of renal damage. Differently from serum creatinine and glomerular filtration rate, which are markers of renal function, increased levels of NGAL in both serum and urine are closely linked to structural damage of the nephron. Clinical studies indicate that within a few hours of occurrence Of acute renal injury serum and urinary NGAL levels are already significantly elevated, while serum creatinine levels and renal clearance only change significantly between 24-48 hours after injury. Thus, the use of renal function markers, usually evaluated in practice, may present some limitations, as well as hinder the application of early measures that aim at renal protection. This review of the literature aims to analyze the biological aspects and applications of NGAL measurement in some clinical conditions, including renal injury, nephropathy and renal ischemia.

Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney damage: a review / Lipocalina associada à gelatinase neutrofílica (NGAL) como um biomarcador de lesão renal: uma revisão

Neutrophil gelatinase- associated lipocalin (NGAL) is a protein molecule predominantly expressed in the distal nephron after the occurrence of renal injury. Unlike the serum creatinine and the glomerular filtration rate, which are the renal function markers, the increased levels of NGAL, both in serum and urine, are closely linked to the structural injury to the nephron. Clinical studies indicate that a few hours after the occurrence of acute renal injury, the serum and urinary levels of NGAL are already significantly elevated, while the serum creatinine levels and renal clearance only undergo significant changes between 24-48h after injury. Thus, the use of renal function markers, usually assessed in the clinical practice, they may have some limitations also hindering the implementation of early measures aimed at protecting the kidneys. This literature review aims at examining the biological aspects and the applications of NGAL measurement in some clinical conditions, including kidney failure, kidney diseases and renal ischemia.

Lipocalina associada à gelatinase neutrofílica (NGAL) é uma molécula proteica predominantemente expressa na parte distal do néfron após a ocorrência de lesão renal. Diferentemente da creatinina sérica e da taxa de filtração glomerular, que são marcadores de função renal, os níveis aumentados de NGAL, tanto no soro quanto na urina, estão intimamente ligados a lesões estruturais do néfron. Os estudos clínicos indicam que poucas horas após a ocorrência da lesão renal aguda os níveis séricos e urinários de NGAL já se apresentam significativamente elevados, enquanto os níveis séricos de creatinina e a sua depuração renal apenas sofrem alterações significativas entre 24-48h após a lesão. Assim, a utilização de marcadores de função renal, usualmente avaliados na prática clínica, pode apresentar algumas limitações além de dificultar a aplicação de medidas precoces que visam a proteção renal. Esta revisão da literatura tem por objetivo analisar os aspectos biológicos e as aplicações da mensuração de NGAL em algumas condições clínicas, incluindo injúria renal, nefropatias e isquemia renal.

Characterization of reactive stroma in prostate cancer: involvement of growth factors, metalloproteinase matrix, sexual hormones receptors and prostatic stem cells.

INTRODUCTION AND OBJECTIVES: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. MATERIALS AND METHODS: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: a-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Era and ERß. RESULTS: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERa. CONCLUSIONS: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.

Characterization of reactive stroma in prostate cancer: involvement of growth factors, metalloproteinase matrix, sexual hormones receptors and prostatic stem cells

ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.