Novel Karyotypes and Cyclin D1 Immunoreactivity in Clear Cell Sarcoma of the Kidney.
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.
1 Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Sze
S
Jet Aw
2 Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
Chik
C
Hong Kuick
2 Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
Min
M
Hwee Yong
2 Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
Derrick
D
Wen Quan Lian
3 Department of Pathology, National University Health System, Singapore.
Shi
S
Wang
4 Department of Pathology, Singapore General Hospital, Singapore.|7 Duke-NUS Graduate Medical School, Singapore.
Alwin Hwai
AH
Liang Loh
2 Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
Sharon
S
Ling
2 Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.
Guat
G
Lian Peh
5 Haematology-Oncology Service, Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore.|7 Duke-NUS Graduate Medical School, Singapore.
Shui
S
Yen Soh
6 Department of Paediatric Surgery, KK Women's and Children's Hospital, Singapore.
Amos Hong
AH
Pheng Loh
1 Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|4 Department of Pathology, Singapore General Hospital, Singapore.|7 Duke-NUS Graduate Medical School, Singapore.
Puay
P
Hoon Tan
2 Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore.|7 Duke-NUS Graduate Medical School, Singapore.
Kenneth
K
Tou En Chang
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000032:analysis*; D003937:Diagnosis, Differential; D005260:Female; D050939:Gene Fusion; D006801:Humans; D007150:Immunohistochemistry; D059785:Karyotype; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011237:Predictive Value of Tests; D018227:Sarcoma, Clear Cell / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D012846:Singapore; D046888:Tissue Array Analysis; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D015514:Oncogene Proteins, Fusion; C576541:YWHAE-FAM22 fusion protein, human; D019938:Cyclin D1
YWHAE-FAM22; clear cell sarcoma of kidney; cyclin D1