Mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II expression in renal cell neoplasms: a tissue microarray and quantitative RT-PCR study.
The kidney is an important target for mineralocorticoids. Aldosterone, the major endogenously secreted mineralocorticoid, acts by binding to mineralocorticoid receptor (MR) in the distal renal tubule. The enzyme 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) prevents the binding of glucocorticoids to the MR by inactivating cortisol to cortisone. Our goal was to determine whether MR and 11beta-HSD2 expression could be used to characterize the major types of renal cell neoplasms. Using immunohistochemistry we analyzed tissue microarray specimens from 132 patients with renal cell neoplasms, stratified into 84 clear cell renal cell carcinomas (CRCC), including 9 cases clear cell carcinoma with predominantly granular cytoplasm; 14 papillary RCC (PRCC); 20 chromophobe RCC (CHRCC); and 14 oncocytomas (OCs). MR and 11beta-HSD2 expression were also quantitated by real-time reverse transcription-polymerase chain reaction. Expression of both MR and 11-betaHSD2 was detected in the distal nephrons of normal kidneys. The CHRCC group stained for 11-betaHSD2 in a membranous and cytoplasmic pattern whereas diffuse cytoplasmic reactivity was seen in OCs. MR and 11beta-HSD2 were coexpressed in most of CHRCC (90% and 95%) and oncocytomas (93% and 100%). No MR staining was detected in CRCC, including clear cell carcinoma with predominantly granular cytoplasm, or in PRCC. Only 2 cases of CRCC (2.6%) showed focal positivity for 11beta-HSD2, whereas all PRCCs were negative. CHRCC and OC demonstrated significantly higher levels of MR and 11beta-HSD2 expression than CRCC and PRCC by real-time polymerase chain reaction. Moreover, CHRCC showed higher expression of MR and 11beta-HSD2, as compared with OC. Our study indicates MR and 11beta-HSD2 are both sensitive and specific markers of the distal nephron and its related neoplasms (CHRCC and OC). Additionally, the staining pattern and the level of MR and 11beta-HSD2 expression seems to be useful in the distinction of CHRCC from OC. MR and 11beta-HSD2 should be considered in the immunohistochemical panel to more accurately subtype renal cell tumors.
Yakirevich
Evgeny
E
Department of Pathology, Rhode Island Hospital, Providence, RI 02903, USA. eyakirevich@lifespan.org
Morris
David J
DJ
Tavares
Rosemarie
R
Meitner
Patricia A
PA
Lechpammer
Mirna
M
Noble
Lelia
L
de Rodriguez
Angela F
AF
Gomez-Sanchez
Celso E
CE
Wang
Li J
LJ
Sabo
Edmond
E
Delellis
Ronald A
RA
Resnick
Murray B
MB
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D018161:Receptors, Mineralocorticoid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2