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

• DOI: 10.2350/14-12-1581-oa.1
• Publication Date: 2015-03-09T21:38:42Z
• Authors: Sze Jet Aw; Chik Hong Kuick; Min Hwee Yong; Derrick Wen Quan ...; Shi Wang; Alwin Hwai Liang Loh; Sharon Ling; Guat Lian Peh; Shui Yen Soh; Amos Hong Pheng Loh; Puay Hoon Tan; Kenneth Tou En Chang
• Keywords: Male; Singapore; Adolescent; Oncogene Proteins, Fusion; Karyotype; Immunohistochemistry; Kidney Neoplasms; Translocation, Genetic; 3. Good health; Diagnosis, Differential; 03 medical and health sciences; 0302 clinical medicine; Predictive Value of Tests; Tissue Array Analysis; Child, Preschool; Karyotyping; Biomarkers, Tumor; Humans; Cyclin D1; Female; Sarcoma, Clear Cell; Gene Fusion; Child

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.