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Argani P, Laé M, Hutchinson B, et al..Renal carcinomas with the t(6;11)(p21;q12). Clinicopathologic features and demonstration of the specific Alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA-PCR

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
American Journal of Surgical Pathology (Impact Factor: 4.59). 03/2005; 29(2):230-40.
Source: PubMed

ABSTRACT A highly distinctive subset of renal neoplasms of children and young adults contains a t(6;11)(p21;q12), a translocation recently been shown to result in fusion of Alpha, a gene on 11q12, with the transcription factor gene TFEB on 6p21. To define the clinicopathologic spectrum of this nascent entity and to establish immunohistochemical (IHC) and molecular methods for the detection of the specific Alpha-TFEB fusion, we studied 7 renal neoplasms that showed the t(6;11) by cytogenetic or molecular analysis (patient age: range, 9-33 years; mean, 17 years). While all tumors were confined to the kidney, 3 tumors demonstrated vascular invasion. In limited follow-up, none has metastasized. We postulated that the Alpha-TFEB gene fusion may result in deregulated expression of TFEB protein that would be detectable by IHC. Using a polyclonal antibody to TFEB on formalin-fixed, paraffin-embedded tissue sections, we found that all 7 renal neoplasms with the t(6;11) demonstrated moderate (2 cases) or strong (5 cases) nuclear TFEB immunoreactivity. In contrast, none of 1089 other tumors (of 74 histologic types from 16 sites) labeled significantly for TFEB. Nuclear immunoreactivity for TFEB in normal tissues was extremely rare, limited to weak labeling of scattered benign lymphocytes. We also show that the Alpha-TFEB fusion RNAs are highly variable in size and structure, making detection by reverse-transcriptase polymerase chain reaction (RT-PCR) less reliable than for other gene fusions. Because Alpha is an intronless gene and therefore lacks splice signals, we hypothesized that DNA PCR and RT-PCR products would be identical, allowing for the use of more robust molecular assays based on genomic DNA. Indeed, in 2 cases with available frozen tissue, we showed the genomic Alpha-TFEB junction detected by DNA PCR to be identical to the Alpha-TFEB fusion mRNA detected by RT-PCR. In summary, renal neoplasms with the t(6;11) are a distinctive neoplastic entity with many similarities to the Xp11 translocation carcinomas, and together with the latter form a growing "MiTF/TFE family" of translocation carcinomas. Nuclear immunoreactivity for TFEB protein is a highly sensitive and specific diagnostic marker for these renal neoplasms. Finally, the special molecular features of the Alpha-TFEB gene fusion allow its molecular detection by DNA PCR as a robust alternative to RT-PCR in clinical tumor samples.

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    • "Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein [10] [11] [12]. Argani et al. [2] detected strong nuclear TFEB labeling in all seven RCCs with t(6;11) translocation studied, in contrast to 1089 other unrelated neoplasms and normal tissues that showed negativity for nuclear labeling of this protein. "
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    ABSTRACT: Introduction Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely rare, fewer than 30 cases have been reported in literature. These tumors are characterized by specific chromosomal translocation involving TFEB, as against the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The distinctive immnohistologic features are helpful in enabling a diagnosis of this rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay, specific for detecting TFEB gene rearrangement. Presentation of case Herein, we report a case of this rare tumor in a 11 years old boy, with the objective of highlighting distinctive light microscopic and immuno-phenotypic features of this rare sub-type of translocation associated renal cell carcinoma, otherwise diagnosed by fluorescence in situ hybridization technique. Morphologically tumor showed distinctive biphasic population of cells, large epitheloid cells with voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of cytoplasm and small rounded nuclei. The smaller cells at places clustered around hyaline pink material forming “pseudorosettes”. population. Immunohistochemically both types of tumor cells showed negativity for pan CK (cytokeratin), EMA (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells) were moderate to strongly expressed. Discussion On review of literature, most RCCs with t(6;11) translocation have been reported to be negative for pan cytokeratins and EMA. Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein. Immunostains for TFE3 have always been negative in the reported cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to misdiagnosis of angiomyolipoma to the unwary. Conclusion Knowledge of distinctive morphological and immuno-histochemical features of this tumor can help in establishing a diagnosis of this rare subset of translocation associated RCC on routine hematoxylin and eosin (H and E) staining and immunophenotyping.
    12/2014; 24. DOI:10.1016/j.ijscr.2014.12.026
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    • "Further, TFEB translocations-associated RCC has been recognized as a newly subtype. This subtype is characterized by nested morphology and immunohistochemical positivity of TFEB [10], which were not observed in the present cases. "
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    ABSTRACT: Although nephroblastoma is the commonest renal tumor of childhood, it is rare in adults. In cases of predominantly epithelial type occurring in adulthood, it might be difficult to distinguish it from papillary renal cell carcinoma and metanephric adenoma. Here, we report three cases of adult epithelial nephroblastoma in 24-, 76-, and 21-year-old females. Histologically, the tumors were composed of papillotubular architectures of small and uniform tumor cells with high nucleocytoplasmic ratio without blastemal element. Immunohistochemically, the tumor cells were positive for WT-1 and CD57 but negative for AMACR, which was helpful to exclude the possibility of papillary renal cell carcinoma. Metanephric adenoma is a benign tumor, which can be distinguished by the observation of the cellular atypism and growth pattern. However, nephroblastoma with predominant epithelial element mimics the malignant counterpart of metanephric adenoma, that is, "metanephric adenocarcinoma."
    09/2013; 2013:675875. DOI:10.1155/2013/675875
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