Loss of BRM expression is a frequently observed event in poorly differentiated clear cell renal cell carcinoma.
OBJECTIVE
The aim of this study was to examine the status of Brahma (BRM), a key SWI/SNF complex subunit, in clear cell renal cell carcinomas (RCCs), and to analyse the histopathology, immunophenotype, molecular features and prognosis of the BRM-negative cases.


RESULTS
We identified 19 cases of grade 4 tumours lacking BRM expression among 625 clear cell RCCs. All 19 cases exhibited features of poor differentiation: 13 showed pure poorly differentiated morphology, while six were composite tumours with an admixed typical low-grade component. Besides negative BRM expression, the immunophenotype of these cases was similar to clear cell RCC. VHL gene mutations were identified in nine of the 19 patients (47%). Chromosome 3p deletion was detected in 11 of 13 poorly differentiated RCCs and both areas of five of five composite tumours. All poorly differentiated tumour areas showed polysomy of chromosome 3. No losses or gains of chromosome 3 were observed in low-grade tumour areas of five of five composite RCCs.


CONCLUSIONS
We have shown that loss of BRM expression is a common feature among poorly differentiated tumours in clear cell RCCs. We hypothesize that loss of BRM expression is involved in tumor de-differentiation in clear cell RCCs and may play an important role during tumour progression.
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Qiu-Yuan
QY
Xia
Qiu
Q
Rao
Liang
L
Cheng
Qin
Q
Shen
Shan-Shan
SS
Shi
Li
L
Li
Biao
B
Liu
Jin
J
Zhang
Yan-Fen
YF
Wang
Qun-Li
QL
Shi
Jian-Dong
JD
Wang
Heng-Hui
HH
Ma
Zhen-Feng
ZF
Lu
Bo
B
Yu
Ru-Song
RS
Zhang
Xiao-Jun
XJ
Zhou
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
C084011:SMARCA2 protein, human; D014157:Transcription Factors
BRM/SMARCA2; SWI/SNF complex; clear cell carcinoma; fluorescence in-situ hybridization; high-grade; immunohistochemistry; poorly differentiated; renal cell carcinoma; rhabdoid; von Hippel-Lindau