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

Abstract

Pathological diagnosis of clear cell sarcoma of the kidney (CCSK) is challenging as it resembles blastemal Wilms tumor (WT) and other pediatric sarcomas, and does not have any distinctive immunophenotype. The YWHAE-FAM22 translocation t(10;17)(q22;p13) has been reported in a subset of CCSK. This translocation also occurs in high-grade endometrial sarcoma, in which it is associated with cyclin D1 overexpression. Hence we seek to determine YWHAE-FAM22 translocation status and cyclin D1 immunoreactivity in a series of local CCSK cases. Of 8 CCSK cases from 7 patients identified, no CCSK had the YWHAE-FAM22 fusion transcript by reverse transcriptase-polymerase chain reaction. Novel karyotypes were identified for 2 cases: 1 had t(2;13)(q13;q22) and the other t(3:17)(q29;p11.2). Excluding a case with poor tissue section antigenicity, 7 of 7 CCSKs (100%) showed diffuse and strong nuclear cyclin D1 staining. Cyclin D1 immunohistochemistry was also performed on tissue microarrays of other pediatric renal tumors: blastemal areas of 18 WT cases were negative; 6 rhabdoid tumors and 1 metanephric adenoma showed patchy and weak staining; 3 mesoblastic nephromas and 18 of 29 neuroblastomas had positive staining. Cyclin D1 immunohistochemistry helps distinguish CCSK from blastemal WT and metanephric adenoma and rhabdoid tumors, but not from neuroblastomas and mesoblastic nephromas. Cyclin D1 overexpression in CCSK is not contingent on YWHAE-FAM22 translocation, and cyclin D1 inhibition may potentially be explored as a targeted therapeutic strategy in CCSK.

Aberrant epigenetic regulation in clear cell sarcoma of the kidney featuring distinct DNA hypermethylation and EZH2 overexpression

“…The trimethylated form of this complex represses gene expression during differentiation and development [ 22 ]. EZH2 also has a PRC2-independent function and can activate expression of cell cycle associated genes such as CCND1 [ 23 ], which is in line with the high expression of cyclin D1 previously observed in CCSK [ 24 ]. The expression of EZH2 has previously been shown to decrease upon kidney maturation in the mouse fetal kidney [ 25 ].…”

Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion

“…2/2 BCOR-CCNB3 soft tissue sarcomas in the current study were positive for TLE1 ** includes data from reference 5 *** includes data from references 3 and 4 **** data from reference 31 ***** data from reference 26 . 1/1 BCOR-CCNB3 soft tissue sarcoma in the current study was focally positive for PAX8…”

“…CCSK may also display a variety of variant morphologic patterns that mimic other neoplasms, including myxoid, sclerosing, cellular, spindled, storiform, palisaded, trabecular, and epithelioid patterns. While cyclin D1 3, 4 and SATB2 5 are often immunoreactive in CCSK, most other immunohistochemical markers such as CD34, S100, desmin, CD99, and cytokeratin are negative.…”

Subpathway-LNCE: Identify dysfunctional subpathways competitively regulated by lncRNAs through integrating lncRNA-mRNA expression profile and pathway topologies

“…HCG-18 competitively regulated another gene CCND1, which was an oncogene acted as a driver of multiple types of human malignancies [46, 47]. CCND1 dysregulation was associated with cellular proliferation and tumor growth of kidney tumor [52]. Another differential hub lncRNA PVT1 was also competitively regulated CCND1 and some other cancer related genes to disturb cancer hallmark pathways including p53 signaling pathway.…”