[1029] Polybromo 1 (PBRM1) Expression in Renal Epithelial Neoplasms (REN) by Immunohistochemistry

Maria Tretiakova, Masha Kocherginsky, Scott E Eggener, Arieh L Shalhav, Tatjana Antic, Gladell P Paner. University of Chicago, Chicago

Background: SWItching and Sucrose Non-Fermenting (SWI-SNF) genes play a key role in chromosomal stability, cellular proliferation and transcription, emerging as bona fide tumor suppressors. Most recently, mutations in PBRM1 gene which encodes BAF180 protein were identified in 41% of renal cell carcinomas (RCC), making PBRM1 the 2nd most frequently mutated gene after VHL (Nature, 2011). Herein, we examined BAF180 expression in a large set of REN using a novel commercially available antibody.
Design: TMA sections of 290 REN (130 clear cell [CCRCC], 79 papillary [PRCC], 52 chromophobe [ChRCC], 4 TFE3 translocation [tRCC] 5 clear cell papillary [PRCC] RCC and 20 oncocytomas [RO]) and 41 normal tissues from different organs including 14 kidneys were immunostained. Anti-BAF180 antibody suitable for paraffin sections was obtained from Sigma (rabbit IgG, 1:160), and tested according to manufacturer's recommendation. Reactivity with >5% of cell nuclei was considered positive, 5-50% - focal, and >50% - diffuse. Staining intensity was scored as weak or strong.
Results: From 290 tumors only 16.5% exhibited nuclear BAF180 reactivity which was strong in 5.5% and weak in 11% of cases. Expression of BAF180 in normal kidney (NK) was present in 57% cases and localized to distal tubules and glomeruli. Detailed BAF180 expression is shown in table 1. Group comparison showed significant difference in BAF180 expression between normal, benign RO and malignant RCC (p=0.019, Fisher exact test) with gradual decrease of % positive cases. This decreasing trend is further confirmed by logistic regression model (p=0.008). Among the 3 RCC histotypes the highest BAF180 expression was in PRCC and lowest in CCRCC (p=0.006).

Type	Negative	Strong diffuse	Strong focal	Weak diffuse	Weak focal
CCRCC	119 (91%)	0	2 (2%)	2 (2%)	7 (5%)
PRCC	60 (76%)	3 (4%)	7 (9%)	5 (6%)	4 (5%)
CHRCC	42 (81%)	0	3 (6%)	2 (4%)	5 (9%)
CPRCC	3 (60%)	0	0	1 (20%)	1 (20%)
tRCC	3 (75%)	0	0	0	1 (25%)
RO	15 (75%)	1 (5%)	0	2 (10%)	2 (10%)
NK	8 (57%)	0	0	3 (21.5%)	3 (21.5%)

Conclusions: Homozygous inactivation of PBRM1 via truncating gene mutations was expected to cause BAF180 expression loss in a significant subset of RCC cases but not in normal kidney or benign tumors. We found statistically significant decreasing trend in BAF180 expression from normal (42.9%) to benign RO (25.0%) to RCC (15.3%), with the lowest BAF180 levels in CCRCC (8.5%). However, overall low frequency of BAF180 expression in vast majority of REN and normal kidney suggest limited value of IHC in predicting mutational status of PBRM1 and warrant further genetic analysis of this promising tumor suppressor gene.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 149, Tuesday Morning