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.