We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed. Antibodies against CK7, CD10, vimentin, epithelial membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase, melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18 females, mean age 24.6 years. Two patients had a previous history of chemotherapy and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5 months. Three patients presented metastases and 5 have died. Mixed papillary and nested patterns with clear and/or eosinophilic cells represented the most consistent histologic appearance, with common foci of calcifications regardless of the type of translocation. Using a 30 mn incubation at room temperature, TFE3 immunostainings were positive in only 82% of our TFE3 translocation carcinomas. Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha-methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was observed in two-third of cases. Cytokeratins were expressed in less than one-third of cases. Melanocytic markers were expressed at least weakly in all cases except two. Unsupervised clustering on the basis of the gene expression profiling indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and alanyl aminopeptidase are the main differentially expressed genes for this group of tumors. Our results suggest that these differentially expressed genes may serve as novel diagnostic or prognostic markers.

Background and Aims: Acute renal failure (ARF) remains a major healthcare problem. Although modern medical therapy has improved its outcome, the syndrome still has high mortality and morbidity rates [Xue et al.: J Am Soc Nephrol 2006;17:1135–1142]. Recently, stem cell (SC) therapies have been proposed as an alternative for the treatment of ARF on the basis of the damaged cells’ replacement or enhanced recovery or regeneration. The aims of this study were to investigate the engraftment of autologous mesenchymal stem cells (MSC) injected into the renal artery in an ovine model of ischemia reperfusion injury (IRI) and to assess the consequence of the delay between injury and cell transplantation on the engraftment. Material and Methods: MSC were transplanted in animals submitted to IRI or in healthy animals not submitted to IRI. Sheep with IRI were grafted at two different time points after injury. Unilateral renal IRI was performed by percutaneous transluminal placement of a balloon catheter in the renal artery. MSC were isolated from bone marrow, cultured, labeled and injected into the renal artery. Results: All ewes showed renal engraftment by MSC, both in tubules and glomeruli. MSC expressed tubular epithelial cell markers and podocyte phenotype. There was a significant increase of engraftment of tubules by MSC when cells were injected early after injury indicating that the delay for cell transplantation after ischemic insult should be short. Conclusions: This is the first report of intra-arterial autologous transplantation of MSC in the kidney, resulting in a successful engraftment into tubular and glomerular structures. The results strongly suggest that the optimal time window for stem cell therapy is during the early phase of the ischemic injury.

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Precise diagnosis of low and high grades of brain tumors permits determining therapeutical strategies. So far, diagnosis and prognosis of gliomas were based on histological and genetic criteria which need being completed by a panel of molecular markers. Highly distributed in brain, gap junction proteins, connexins, could be considered as markers of glioma progression as previous studies indicated that expression of a connexin type, connexin43 (Cx43), is inversely correlated to tumor grading. However, this assumption was weakened by the low number of glioma samples used. Taking advantage of tissue microarray technique, we pursued this analysis by studying in situ expression of Cx43 on 85 samples (37 grade IV, 18 grade III, 24 grade II, and 6 grades II to III). Our analysis confirmed the global diminution of Cx43 expression in glioblastomas that was observed in previous studies. However, this analysis brought new insights such as the following ones. First, the high number of samples permitted to show that more than 60% of glioblastomas still express Cx43. Second, no gradual decrease in Cx43 expression was observed between grades II and III, but Cx43 appeared to be a marker distinguishing oligodendrocytic and astrocytic grade III tumors. Third, independently from tumor grade, a Cx43 nuclear staining was detected in areas where leukocytes are present. In conclusion, our study emphasizes the importance of in situ immunohistochemical approaches by giving more precise insights in the subcellular localization of Cx43. It also emphasizes the necessity to carry out such analysis on a wide range of samples to circumvent the high glioma heterogeneity.

To evaluate a possible implication of cytokines in the pathogenesis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, we studied five consecutive patients with this condition, of which four had sclerotic bone lesions and four had multicentric Castleman's disease. Interleukin-1 beta (IL-1 beta) and IL- 6 serum levels were determined in these patients (13 serum samples) and in patients with multiple myeloma (5) and Waldenstrom's macroglobulinemia (5). In situ hybridization of the relevant mRNAs was performed on lymph node specimens of two patients with POEMS syndrome who had Castleman's disease. Elevated serum levels of IL-1 beta (13/13 samples), and IL-6 (7/13 samples) were found in patients with POEMS syndrome. In the other patients, serum IL-1 beta was undetectable or slightly increased and IL-6 was elevated in a single patient with Waldenstrom's macroglobulinemia. Abundant IL-1 beta mRNA-producing cells were present in interfollicular spaces in the two tested patients, while IL-6 mRNA-producing cells were rare. We conclude that IL-1 beta and IL-6 serum levels may be chronically elevated in patients with POEMS syndrome, and that lymph node may be one site of IL-1 beta overproduction. These results are in keeping with the hypothesis that cytokines mediate systemic manifestations of POEMS syndrome.