Clear Cell Sarcoma of Kidney: Morphoproteomic Analysis Reveals Genomic Correlates and Therapeutic Options

Abstract

Results: The results of immunohistochemistry and EBER are shown in the table. Survivin and Bax were expressed strongly in all the cases, and the pattern of staining was both nuclear and cytoplasmic. No apparent correlation was seen between the expression of EBER and p5. CC p5 Bax Survivin Bcl-2 EBER Absent 56% 6% 0% 0% 6% 64% Weak 42% 92% 0% 0% 5%-Strong 2% 2% 100% 100% 2% 6% Conclusions: Our study demonstrates abnormalities in the apoptotic pathways in HRS cells in pediatric cHL. Down-regulation of p53 may contribute to the over-expression of survivin, which then suppresses the final apoptosis effector CC3 and contributes to the resistance of HRS cells to apoptosis, despite the strong expression of the upstream Bax. Survivin may therefore be a potential target for the treatment of pediatric cHL. Background: Neuroblastoma (NB) is a pediatric solid tumour with a poor outcome except in children younger than one year. Based on catecholamines urinary excretion, several mass screening programs have been organised in infants. The AKT pathway contributes to tumor aggressiveness in many cancers. The objective was to analyse expression AKT activation in between mass screening NBs in comparison to standard NBs. Design: A first tissue microarray with standard NB was performed with 101 primary tumors and 39 paired metastases (median age of 30 months (range, newborn to 151 months, 16 stage 1, 7 stage 2, 22 stage 3, 48 stage 4 and 8 stage 4S). A second tissue microarray with mass screening NB coming from Quebec and Japan contained 55 primitive tumors and 21 metastases (median age of 7 months (range 1 to 14 months), 16 stage 1, 15 stage 2, 9 stage 3, 6 stage 4 and 9 stage 4S). Immunohistochemical staining was performed using antibodies against, AKT, phosphoAKT and TRKB which is known as a poor prognosis factor of NB. Immunostaining intensity was evaluated by a semi-quantitative score based on the percentage of positive cells. The t-student test was applied for the comparison of protein expression between standard and mass screening NB. Results: The expression of phosphoAKT was significantly higher in primitive tumors, in metastases, in stage 1 and in patient under one year of standard NB (mean intensity 1.92, 2.1, 1.54 and 1.97 in 96%, 92%, 94% and 100% of tumors cells, receptively) than in mass screening NB (mean intensity 1.18, 1.05, 0.96 and 1.22 in 75%, 68%, 62% and 78% of tumors cells, receptively). AKT was only significantly more present in primitive and metastases of standard NB than in mass screening NB, as for TRKB. Conclusions: The activation of AKT pathway is significantly higher in standard than in mass screening NB independently of age, stage and primitive of metastatic status of the tumor. This confirmed that NB diagnosed through mass sceening differ biologically from standard NB. Background: Ewing's sarcoma (ES), a highly aggressive pediatric tumor is associated with translocations that fuse the EWS gene to one of the ETS family of genes/ transcription factors.The resultant fusion proteins effect transcriptional...

Novel Karyotypes and Cyclin D1 Immunoreactivity in Clear Cell Sarcoma of the Kidney

“…Because none of our CCSK had the YWHAE-FAM22 translocation, cyclin D1 overexpression in CCSK likely results from a different mechanism, possibly involving upregulation of the Sonic Hedgehog pathway. In a study of 3 cases of CCSK, what the authors term a “morphoproteomic analysis” (essentially a immunohistochemical survey) of the sonic hedgehog, nuclear factor kappa B (NF-κB), and mammalian target of rapamycin pathways showed involvement of these pathways, explaining cyclin D1 overexpression on this basis [5]. Gene expression profiling studies of CCSK have demonstrated upregulation of neural markers and activation of the Sonic Hedgehog and PI3K/Akt pathways with upregulation of PTCH, GLI1, GLI2, TWIST1, PDGFRA, PDGFA , and CCND1 [6].…”

“…Clear cell sarcoma of the kidney lacks a distinctive immunophenotype, and the cell of origin of CCSK is not clear. Recent reports suggest that nerve growth factor receptor (NGFR) and cyclin D1 immunoreactivity may be used to support a diagnosis of CCSK [5,6]. However, NGFR is not an immunohistochemical stain that is widely available in most pathology departments at present.…”

Expression of cyclin D1 in clear cell sarcoma of kidney. Is it useful in differentiating it from its histological mimics?

“…Molecular tests for detecting BCOR gene abnormalities are not available especially in developing countries such as ours. Recently, a number of studies have suggested that immunohistochemical stain Cyclin D1 is useful in distinguishing CCSK from some pediatric renal neoplasms [3, 5, 19]. More importantly, recent studies suggest that BCOR immunohistochemistry appear to be highly sensitive and specific for the diagnosis of CCSK based on the recently identified BCOR gene abnormalities.…”

Revealing the role of VEGFA in clear cell sarcoma of the kidney by protein-protein interaction network and significant pathway analysis

“…Over the previous decades, genetic studies regarding CCSK have been limited and the underlying mechanism of the disease consequently remains unclear. Dhamne et al ( 5 ) reported that cyclin D1 (CCND1) may be a central molecule in the pathogenesis of CCSK, primarily regulated by nuclear factor κB (NF-κB) cells. Forkhead box D1 and cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain 1, are highly expressed in CCSK, with oxidative-stress-responsive kinase 1, an early embryonic marker, also expressed at high levels in CCSK and at greater levels than observed in normal kidneys or Wilms' tumors (WT) ( 6 ).…”