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OBJECTIVES: The aim of this study was to evaluate the reactivity of steroid hormone receptors (SHRs), dystroglycans (DGs), matrix metalloproteinases (MMPs), insulin-like growth factor receptor (IGFR-1), and laminin (Lam) in both prostatic stromal and epithelial compartments showing different diseases in elderly men. METHODS: Sixty prostatic samples were obtained from 60- to 90-year-old patients (mean 63 years) with and without prostatic lesions from Hospital of the School of Medicine, State University of Campinas (UNICAMP). The Samples were divided into standard (no lesions); high grade prostatic intraepithelial neoplasia (HGPIN); prostatic cancer (PC); and benign prostatic hyperplasia (BPH) groups. The samples were submitted to immunohistochemistry and Western blotting analyses. Research Ethics Committee of the School of Medicine, University of Campinas/UNICAMP (number 0094.0.146.000-08). RESULTS: The results showed increased IGFR-1 and MMPs protein levels in the PC and HGPIN groups. Decreased αDG and ßDG protein levels were verified in the PC and HGPIN groups. Androgen receptor (AR) reactivity was similar among all groups. Estrogen receptor α (Erα) immunoreactivity was more intense in the epithelium in the PC and HGPIN groups. Estrogen receptor ß (ERß) immunoreactivity was weak in the epithelium of the HGPIN and PC groups. CONCLUSIONS: To conclude, there was an association among IGFR-1, MMPs, and SHRs, indicating IGFR-1 as a target molecule in prostate therapy, considering the IGF proliferative properties. Also, the distinct SHRs reactivities in the lesions in both prostatic compartments indicated different paracrine signals and pointed out the importance of estrogenic pathways in the activation of these disorders.

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OBJECTIVE: There is no consensus for grading when more than one grade is present in bladder carcinoma. We propose a grading system that considers the primary (most common) and secondary (second most common) grade of bladder cancer. Grade was correlated with stage of the tumors. MATERIAL AND METHODS: We studied 293 bladder transurethral resections or radical cystectomies. Grade was considered as 1, 2 or 3 according to the 1999 World Health Organization system. The number was repeated when only one grade was seen. A final score was obtained which ranged from 2 to 6. All cases were also graded according to the highest grade area even if it was focal. RESULTS: According to the highest grade area, the distribution was 80 (74.07%), 27 (25.00%) and 1 (0.92%) for grade 1; 31 (24.03%), 69 (53.48%) and 29 (22.48%) for grade 2; and 0 (0%), 17 (30.35%) and 39 (69.64%) for grade 3, corresponding to the stages Ta, T1 and T2-T3, respectively. Using the system of combined numbers, grade 2 was stratified into subgroups 1 + 2 and 2 + 2 which are statistically different (p < 0.05) when considering stage. In grade 3, there was also a trend for statistical difference (p = 0.066) between grades 2 + 3 and 3 + 3. CONCLUSIONS: The grading system of combined numbers, stratifies grade 2 into subgroups 1 + 2 and 2 + 2, and grade 3 into subgroups 2 + 3 and 3 + 3 which are statistically different when considering stage. This grading system of combined numbers takes into consideration tumor heterogeneity and may be of value in prospective studies for analysis of prognosis and therapeutic response.

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BACKGROUND: It is controversial if urothelial carcinoma of the bladder with squamous and/or glandular differentiation is a more aggressive neoplasm than conventional urothelial carcinoma. DESIGN: A total of 165 transurethral resections of the bladder were reviewed. A group with squamous and/or glandular differentiation was compared to a group without this finding. The chi-square test was used to assess the association of the groups with stage (TNM, 1997). RESULTS: Of the total of 165 transurethral resections of the bladder, 153 (92.72%) were conventional urothelial carcinomas and 12 (7.27%) showed squamous and/or glandular differentiation. The distribution according to stage was 84 (54.9%), 35 (22.9%) and 34 (22.2%) for the group without differentiation and 0 (0%), 3 (25%) and 9 (75%) for the group with squamous and/or glandular differentiation, respectively for stages pTa, pT1 and pT2. Tumors with squamous and/or glandular differentiation showed a significant statistical correlation to higher stage at clinical presentation (p < 0.0001). There was no significant statistical relation according to age (p = 0.8433), sex (p = 0.5672) or race (p = 0.3137). CONCLUSIONS: The results suggest that urothelial bladder carcinomas with squamous and/or glandular differentiation are more aggressive neoplasms. There was a significant statistical correlation between tumors with this differentiation and higher stage at clinical presentation.

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BACKGROUND: Elastosis of the prostate may be seen on needle biopsy and radical prostatectomy specimens, but its significance is unknown. Prostatic atrophy (or postatrophic hyperplasia) is one of the most frequent mimics of prostatic adenocarcinoma. OBJECTIVE: To observe the frequent occurrence of elastosis of the prostate stroma in areas of postatrophic hyperplasia. DESIGN: A step-section method was used to cut the posterior lobe (or peripheral zone) in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsy specimens of men older than 40 years. Elastosis was detected because of a basophilic tinge of the stroma on hematoxylin-eosin stain and confirmed using elastic fiber stains. Presence of elastosis correlated with the following variables: age, prostatic atrophy (simple, hyperplastic, or sclerotic), local arteriosclerosis, histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. For statistics, a stepwise linear regression method adjusted for age was used. RESULTS AND CONCLUSIONS: Elastosis was found in 65 of the prostates examined and was significantly more frequent with increasing age (P <.001), prostatic atrophy (P <.001), and local arteriosclerosis (P <.02). There was no significant relation to histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. The correlation with local arteriosclerosis favors a possible role of ischemia to its etiopathogenesis. The absence of correlation to neoplastic and preneoplastic lesions and the striking spatial relationship of elastosis to prostatic atrophy (or postatrophic hyperplasia) add a new microscopic feature for the diagnosis of this latter lesion, helping in the differential diagnosis with prostate adenocarcinoma.

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Assuntos

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Prostatic atrophy (PA) is one of the most frequent mimics of prostatic adenocarcinoma. It occurs almost exclusively in the peripheral zone of the gland and gained importance with the increasing use of needle biopsies for the detection of prostatic carcinoma The etiopathogenesis is unknown, and there is controversy related to the potential of PA as a precancerous lesion. The frequency increases with age. Compressions caused by hyperplastic nodules, inflammation, hormones, nutritional deficiency, or systemic or local ischemia, are all possible factors in the pathogenesis of PA. The peripheral zone of the prostate was step-sectioned and totally embedded from the bodies of 100 consecutively autopsied men more than 40 years of age. The fragments were microscopically studied for presence of PA, latent (histologic) carcinoma, high-grade prostatic intraepithelial neoplasia, local arteriosclerosis, and prostatitis. The prostates were macroscopically examined for the presence of nodular prostatic hyperplasia. The autopsy reports provided information concerning the presence of generalized atherosclerosis and benign or malignant nephrosclerosis. PA was seen in 85 of the 100 prostates examined and histologically was subtyped into simple, hyperplastic, and sclerotic atrophy. In 65 (76.47%) of 85 cases, the histologic subtypes were combined. In 33 (50.76%) of these 65 cases, the three subtypes were seen concomitantly, favoring the hypothesis that they represent a morphologic continuum of only one lesion. Fibrosis of the stroma may or may not be present in simple and hyperplastic atrophy. Hyperplastic atrophy associated with fibrosis of the stroma is the histologic subtype that most frequently mimics adenocarcinoma Sclerotic atrophy always presents fibrosis of the stroma. PA increases with age, and, in our study, ischemia caused by local intense arteriosclerosis seems to be a potential factor for its etiopathogenesis. Because there was no relation to latent (histologic) carcinoma or high-grade prostatic intraepithelial neoplasia, PA is probably not a premalignant lesion.

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Chromophobe renal cell carcinoma (CRCC) may be grossly and microscopically confused with oncocytoma. It is now believed that many, if not all, of the so-called malignant oncocytomas or oncocytomas with metastases reported in the literature were indeed chromophobe renal cell carcinomas. CRCC is characteristically positive for colloidal iron and shows cytoplasmic microvesicles in electron microscopy. This study of CRCC is thought to be the first one done in Latin America. Of a total of 106 renal epithelial neoplasms, 7 (6.6%) fulfilled the criteria for chromophobe renal cell carcinoma. This frequency in Brazil is similar to that in other parts of the world. There was no difference in age, sex, and race distribution of CRCC compared to usual renal epithelial tumors. Grossly, the CRCC ranged in size from 3.5 to 20 cm (average: 10.2 cm) in greatest dimension. Most frequently, the tumor was brown on the cut surface. The growth pattern showed compact areas in all tumors and, in most of the cases, both clear and eosinophilic cellular subtypes were seen. The electron microscopic findings favor an origin of the microvesicles from outpouchings of the outer membrane of mitochondria. The strong positivity for colloidal iron in spite of the destruction of the cytoplasmic vesicles in paraffin-embedded specimens seems to indicate that the acid mucopolysaccharides are not located inside the microvesicles. By the time of diagnosis, only one case had regional lymph node metastases and this particular case was the only one mixed (associated with the usual renal cell carcinoma). The follow-up examination after nephrectomy showed that prognosis seems to be favorable in CRCC, except when the tumor coexists with the usual renal cell carcinoma.

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Twenty-eight cases of transitional cell carcinomas, (19 papillary cell carcinomas, 9 nonpapillary invasive carcinomas) with concomitant mucosal biopsies are reported. Multiple biopsies were obtained cystoscopically at diagnosis (during resection or biopsy of the main tumor) or afterwards, during post-operative evaluation. Fifteen patients (53.6%) were positive for dysplasia, carcinoma "in situ" or micro-invasive carcinoma in the biopsies. These lesions were correlated with the primary neoplasm in regard to: 1) histological grade. Atypical lesions were more frequent the higher the grade (0.01 < p < 0.05); 2) clinical staging. The possibility of finding atypical lesions was higher in cases with more advanced staging (0.01 < p < 0.05) and 3) presence of one or more tumors visible cystoscopically. The results were not statistically significant (0.10 < p < 0.50) but there was a trend toward a higher incidence of atypical lesions among patients with more than one tumor at cystoscopy. Performance of multiple mucosal biopsies is the only means of diagnosing for atypical lesions of the bladder because, due to their plane configuration, they are not detected cystoscopically. The presence of these lesions is very important because they influence the prognosis and the therapeutic measures.

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The effects of BCG in the treatment of superficial bladder cancer in man are known, but the mechanism is not quite well understood. Thirty-six hamsters received BCG through three routes: intravesical, intradermal and oral. Each group was composed of 12 animals; BCG was administered to 9 and only saline solution to 3 hamsters. BCG was given once a week for six weeks. The animals were sacrificed at 20, 30 and 65 days after the last administration of BCG. The anatomopathologic study revealed granulomatous reaction in the liver of 5 hamsters and in the spleen of 4 other animals of the intravesical group. In all groups that received BCG, hyperplasia of periarteriolar lymphoid tissue (T zone) of the spleen was observed. We support the view that BCG promotes a systemic reaction whatever the route of administration may be.

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A 29-year-old man had oedema, proteinuria in nephrotic range, haematuria and cardiac arrhythmia (second grade atrioventricular block). The pathologic findings of kidney biopsy showed in light microscopy diffuse mesangial matrix increase with mild mesangial proliferation and variable thickening of the glomerular capillary walls. IgG, c3 and c1q were intensely fluorescent and exhibited a diffuse granular pattern in mesangial areas and along the capillary walls. Both kappa and lambda chains were weakly positive in the same pattern. Ultrastructurally, microfibrils of about 20 nm in width were seen to be deposited in mesangial areas and along the glomerular basement membranes. Congo red stain and metachromasia were negative. Neither cryoglobulinaemia nor paraproteinaemia including light chains were found. The aetiology of nonamyloidotic fibrillary glomerulopathy is unknown and no clear-cut clinical or pathologic pattern has emerged. It may represent more than one disease process with a common morphologic expression.

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