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Introduction: Papilar adenocarcinoma of endolymphatic sac is related with Von Hippel Lindau disease at 15% of cases, has a slow growing with a high local aggressiveness, and doesn't metastasize. It causes symptoms of Meniere's syndrome due to the compression that produces at endolymphatic duct. When it presents with hearing loss is usually sudden and irreversible manner. The diagnostic is made with image tests and analysis of its structure with immunohistochemical tests. The elective treatment is surgical remove, and its main complication the perioperative bleeding it can be avoided with preoperative embolization or stereotactic radiation., Case Report: A case of endolymphatic sac tumour is presented, in a 17-years-old male with unilateral deafness and crisis of rotate vertigo, with family history of Von Hippel-Lindau disease. Perceptive deafness and right vestibular arreflexia are detected at technical exploration. In a petrous bone computer tomography appears a mass at vestibular aqueduct. We performed a petrosectomy with presigmoidal approach and saving of inner ear. Pathological analysis revealed an endolymphatic sac tumour., Discussion: In patients with a family history of Von Hippel Lindau disease and clinical symptoms of vertigo and normal hearing or with slight hearing loss we should suspect the presence of endolymphatic sac tumor. The clinical presentation of hearing loss can be sudden and irreversible even with negative or inconclusive images. Therefore, a quick action is important for the preservation of this function.

We determined whether ubiquitylation and sumoylation processes are involved in conventional renal cell carcinogenesis associated with chronic, long-term, persistent low doses of ionizing radiation (IR) in patients living for more than 20 years in cesium-137 ((137)Cs)-contaminated areas after the Chernobyl accident in Ukraine. To this end, we assessed the immunohistochemical expression of ubiquitin (Ub), SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle regulators p53, mdm2, and p14(ARF) in 38 conventional renal cell carcinomas from Ukrainian patients with different degrees of radiation exposure after the Chernobyl accident. As control cases, 18 conventional renal carcinoma (cRCC) tissues from a Spanish cohort were analyzed. No significant differences between the Ukrainian and Spanish groups were found regarding Ub overexpression, although being higher in the Ukrainian cases. Furthermore, this expression was inversely associated with SUMO1 and Ubc9, with no correlation with tumor nuclear grade. There was also a direct relationship between Ubc9 and inflammatory response. These findings do not allow us to consider the immunohistochemical expression of ubiquitylation and sumoylation as valuable markers for discriminating the effects of long-term, low-dose IR exposure in cRCC carcinogenesis.

The present study was carried out in order to examine molecular alterations of extracellular matrix (ECM), associated with cell-cell communication in conventional (clear-cell) renal cell carcinomas (cRCCs) influenced by persistent long-term, low-dose ionizing radiation (IR) exposure to patients living more than 19 years after the Chernobyl accident in Cesium 137 (137Cs)-contaminated areas of Ukraine. The ECM major components such as fibronectin, laminin, E-cadherin/beta-catenin complexes and p53 tumor suppressor gene protein, and transforming growth factor beta 1 (TGF-beta1) were immunohistochemically (IHC) evaluated in cRCCs from 59 Ukrainian patients, which represented 18 patients living in non-contaminated areas and 41 patients from 137Cs-contaminated areas. In contrast, a control group of 19 Spanish patients with analogue tumors were also investigated. For IHC evaluation, a tissue microarray technique was used. Decrease or loss and abnormal distribution of fibronectin, laminin, E-cadherin/beta-catenin complexes accompanied by elevated levels of p53 and TGF-beta1 were detected in the Ukrainian cRCCs from 137Cs-contaminated areas with statistically significant differences. Thus, our study suggests that chronic long-term, low-dose IR exposure might result in global remodeling of ECM components of the cRCCs with disruption in peri-epithelial stroma and epithelial basement membranes.

Compared to the 19-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in the Ukraine has increased from 4.7 to 9.0 per 100,000 of the total population. Cesium 137 ( 137 Cs), which accounts for 90% of the internal radioactivity in the Ukrainian population exposed to long-term low-dose radiation and 90% of the more labile pool of 137 Cs, is excreted via the kidneys. Our present study aimed to evaluate the status of pro- and anti-apoptotic regulatory molecules in conventional renal cell carcinomas (cRCCs) in Ukrainian patients. To achieve this objective, Bcl-2, Bcl-x, BAX, death receptor (DR5) and transcriptional nuclear factor kappa B (NF-κB, with p50 and p65 subunits) were immunohistochemically investigated using a tissue microarray technique in cRCCs from a group of 56 Ukrainian patients, comprising 18 patients living in non-contaminated areas and 41 patients from 137 Cs-contaminated areas. As a comparison, 19 Spanish patients with analogous tumors were also investigated. It was shown that BAX and DR5-positive cRCCs tended to increase among the Ukrainian patients living in the radio-contaminated areas, along with the suppression of anti-apoptotic molecules (Bcl-2 and Bcl-x) and with p65 and p50 overexpression in the same tumors. This study suggested that chronic long-term, low-dose radiation exposure might result in the alteration of the apoptotic regulatory mechanisms, which, in turn, could lead to enhanced tumor progression and resistance to apoptosis., (Copyright© 2006 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved.)

Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15(INK4B)) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 ((137)Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14(ARF) and p16(INK4A) genes, associated with increased p38MAPK, p14(ARF), mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation.

Unlabelled: A retrospective study was performed to determine the prognostic value of Basement Membrane (BM) integrity, Matrix Metalloproteinases (MMPs) and E-Cadherin expression in renal cell carcinoma (RCC)., Materials and Methods: An immunohistochemical study on laminin and collagen IV, MMPs 1 and 2, and E-Cadherin was carried out on 71 RCCs. BM fragmentation was considered taking 75% as a cut-off. MMP 1 and MMP2 immunostaining, as well as E-Cadherin was considered taking 25% as a cut-off., Results: An inverse relationship was seen between E-Cadherin with laminin, collagen IV and MMPs. More than 75% loss of laminin, collagen IV and E-Cadherin, as well as higher expression of MMPs, were associated with symptoms, tumoral size and worse grade. Loss of collagen IV and E-Cadherin were of prognostic value., Conclusion: Both BM and E-Cadherin are good prognostic markers. MMPs patterns show a relationship between BM proteins and E-Cadherin, but evaluation is more time-consuming and provide no better prognostication; consequently they are not useful in routine clinical applications.

Our study was undertaken to better understand the role of G1/S transition abnormalities in the malignant progression of renal cell carcinomas (RCCs), exposed to long-term low doses of ionizing radiation (IR), from patients living in radiocontaminated areas of the Ukraine after the Chernobyl accident. We studied p16 and p15 gene alteration in association with oxidative stress markers, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). We analyzed 88 samples collected from 22 patients with RCCs and with different exposure to IR. Homozygous deletion of the p16 and p15 genes, as well as hypermethylation of the 5CpG island in the promoter region of the same genes, were analyzed by differential PCR and Methylation-Specific PCR respectively, in association with histopathology and immunohistochemical analysis of p16 and p15 proteins. COX2 and iNOS expression in the same tumors were likewise analyzed. Aberrant hypermethylation was observed in 7 (32%) and 5 (23%) cases accompanied, by immunohistochemical loss of expression for p16 and p15 genes respectively, in both high stage and grade tumors from patients living in radiocontaminated areas, this being especially outstanding for the p16 gene. An association with COX2 and less iNOS overexpression in the same tumors was observed. Our data suggest that inactivation of p16 gene, but not p15, induced by increased oxidative stress generated by persistent chronic exposure to IR, could be one of the major pathways responsible for RCCs malignant progression.

Objectives: To know the basal membrane (BM) integrity in renal cell carcinoma (RC) and its importance as prognostic factor., Material and Methods: 73 patients with RC were selected. Immunohistochemistry with monoclonal antibodies against basal proteins laminin and collagen IV was performed. Percentage for BM fragmentation in the whole tumour was considered taking 75% as cut off., Results: Follow-up was 6.3 +/- 4.3 years and 27 patients progressed. Correlation between laminin and collagen IV was significative (p = 0.000). A BM fragmentation expressed with laminin bigger than 75% was related to tumoural symptoms (p = 0.019), worse grade (p = 0.004) and necrosis in more than 10% of the tumour (p = 0.000). Fragmentation observed with collagen IV was associated to tumours greater than 7 cm (p = 0.014). Those patients whose tumours displayed more than 75% of BM fragmentation, measured with collagen IV, presented worse survival (p = 0.042). A similar trend was observed in the case of laminin, but it did not reach statistic significance (p = 0.119). In the unvariated analysis grade III-IV, more than 10% of necrosis within the tumour, tumoural symptoms and BM fragmentation bigger than 75% measured with collagen IV were prognostic, while only grade and necrosis did so in the multivariate analysis., Conclusions: Collagen IV and laminin represent nicely, with a similar expression pattern, the BM fragmentation in RC. Within a battery of immunohistochemical markers to study RC at least one of them should be included because their prognostic implication.

Background: A retrospective study was performed on patients with renal cell carcinoma to determine whether tumoral proliferating cell nuclear antigen (PCNA) is a predictive factor., Methods: We studied immunohisto-chemical PCNA expression with pc10 monoclonal antibody in 109 renal tumor paraffin sections. These tumors were previously classified according to cellular type by Thoenes, Furman's grading and Robson's staging, Moreover, we counted the number of mitoses in 10 high power fields (HPF) and also evaluated the tumoral necrosis percentage. Ten year survival curve of Kaplan and Meier was obtained for 90 patients., Results: Nuclear immunostaining for PCNA showed a statistical correlation with Robson's stage, cellular type and nuclear grade. Moreover, the number of positive nuclei was higher in tumors presenting an elevated mitosis count and higher in degree of necrosis. Survival was significantly poorer in patients whose PCNA index was greater than 5%. Nuclear PCNA immunostaining was shown to be an independent prognostic factor in patients with Robson stage I and also in those who had high cytological grading., Conclusions: These results show PCNA to be a prognostic marker for RCC.

A case of chromophobe renal cell carcinoma is reported in a 73 year-old man. Light microscopically, the tumor was composed of polygonal cells with a slightly eosinophilic and a fine reticular pattern, and a reaction of the cytoplasm with Hale's acid iron colloid. Ultrastructural analysis showed membranous microvesicles within the tumor cells, with degenerated mitochondria. Immunohistochemical profile against intermediate filaments was positive to cytokeratin 18 and negative against vimentin. Flow cytometry and cytogenetics revealed a predominant hypertriploid population. Few cases have been published with flow cytometry and cytogenetic findings. We report a new case.

Three Bellini duct carcinomas (BDC) of the kidney were cytogenetically analyzed after short-term culture. All three had clonal chromosome abnormalities: 91-92,XXY,-Y, +12, +12, -15, -16, -18, +mar (case 1); 53,XY, +2,t(2;7)(p22;q11), +der (2)t (2;7)(p22;q11), +3, +r(3),add(5)(p15), +7, -8, +12, +17, +r(17), +20, -21 (case 2); and 44-47,X,-Y, +9, +16, -21/46,XY. Some of the numerical abnormalities are shared with papillary renal cell carcinomas (PRCC)(+7, +12, +16, +17, and +20) but not with transitional renal cell carcinomas. The present findings support the previous notion that BDC are different from other types of RCC.

Results of an immunohistochemical study in normal urothelium and transitional cell carcinomas of the bladder are presented. Paraffin-embedded material was confronted with immunoantisera against carcinoembryonic antigen (CEA), keratin (K), cytokeratin (CK) and epithelial membrane antigen (EMA). Immunohistochemical findings confirm the changes in reactivity of dysplastic urothelium and carcinoma in situ for CEA, CK and EMA, in comparison with normal urothelium. Statistically significant differences were also found, depending upon tumor stage, in staining of transitional cell carcinomas for K and CK. Expression of CK correlated with the tumor differentiation grade: normal urothelium and well-differentiated carcinomas showed a specific pattern of immunostaining for the basal cells, this pattern being lost in poorly differentiated carcinomas.

We present six female patients aged 14 to 47, all diagnosed histopathologically as suffering from Ask-Upmark Kidney and who had clinical manifestations of severe arterial tension associated with urinary infection in four cases. Mictional Cystourethrography was carried out in all cases, and four of them displayed vesicoureteral reflux in the small kidney. Although this pathology has classically been considered a congenital malformation in the context of renal hypoplasias (segmental hypoplasia), the observation of glomerular traces with PAS staining in the renal segments regarded classically as "aglomerular" and the frequent association of this pathology with vesicoureteral reflux point significantly towards Ask-Upmark Kidney being a form of reflux nephropathy. Nephrectomy cured the arterial hypertension in half the cases, and the factors with prognostic importance in this respect are commented upon.

We present a fresh case of adenomatous polyp with prostatic type epithelium located in the vesical neck, with urethral orientation, in a 59-year-old male. The interest lies in that it is a relatively uncommon lesion, which generally starts off with hematuria, thus causing vesical carcinoma to be suspected, and which in our case displayed recurring capacity despite confirmation of its benign characteristics.