Expression of the Glucocorticoid Receptor in Renal Cell Neoplasms: Diagnostic, Histogenetic, and Prognostic Implications
E Yakirevich, A Matoso, DJ Morris, R Tavares, E Sabo, RA DeLellis, MB Resnick, LJ Wang. RI Hospital and the Alpert Medical School of Brown University, Providence, RI
Background: Glucocorticoids (GCs) are steroid hormones involved in a variety of physiologic and pathologic processes, such as cellular differentiation, growth, inflammation, and the immune response. GCs mediate their effect by binding to the glucocorticoid receptors (GRs), members of the steroid hormone receptor superfamily, which are expressed in a variety of target tissues, including the kidney. Our goal was to determine the expression pattern and prognostic significance of GR in renal cell neoplasms (RCNs).
Design: Paraffin embedded microarray specimens from 187 consecutive patients with RCNs were analyzed for GR expression by IHC. A rabbit polyclonal Ab PA1-511A from Affinity Bioreagents was used as the primary Ab. Cases were stratified into 132 clear cell renal cell carcinomas (CRCC), 25 papillary RCC (PRCC), 16 chromophobe RCC (CHRCC), and 14 oncocytomas (OC). The intensity of protein expression was scored semiquantitatively on a scale of 0-3+.
Results: Strong nuclear GR expression was present in normal renal glomeruli and in the proximal convoluted tubules, whereas distal convoluted tubules and collecting ducts were negative. In the RCNs the staining pattern was similar to that in normal kidney with predominant nuclear GR localization. GR expression was found in the majority of CRCC (68%), in 24% of PRCC, and in only 6% of CHRCC and 14% of OC (P<0.005). Within the CRCC group the vast majority of positive cases (88%) demonstrated strong nuclear reactivity (2+ and 3+), whereas none of the CHRCCs and OCs showed strong expression. Univariate analysis revealed a significant direct correlation between GR expression and overall survival in the CRCC group (P=0.03). By the end of follow-up 88% of CRCC patients with positive GR staining were alive as opposed to 59% of the patients whose tumors were negative. Multivariate analysis indicated that GR expression was an independent predictor of survival (P=0.04).
Expression of GR in RCNs
|Positive||90/132 (68%)||6/25 (24%)||1/16 (6%)||2/14 (14%)|
|Strong (2+-3+)||79/132 (60%)||1/25 (4%)||0/16 (0%)||0/14 (0%)|
Conclusions: The majority of CRCC strongly express GR, distinguishing them from CHRCC and OC. This expression pattern reflects the histogenetic origin of CRCC from the proximal nephron. GR may be considered in the IHC panel to more accurately subtype RCNs. Moreover, GR expression proved to be a strong predictor of patient survival in CRCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 110, Wednesday Afternoon