Expression of the Na+/K+-Transporting ATPase Gamma Subunit FXYD2 in Chromophobe Renal Cell Carcinoma and Renal Oncocytoma
Joseph P Gaut, Dan L Crimmins, Christina M Lockwood, Jay J McQuillan, Jack H Ladenson. Washitngton University School of Medicine, St. Louis, MO
Background: Chromophobe renal cell carcinoma (RCC) is a deadly form of renal cancer that is histologically similar to the benign renal oncocytoma. There are no robust markers available to distinguish these neoplasms. Chromophobe RCC and renal oncocytoma are presumably derived from the distal nephron. FXYD2 is a distal tubule protein that is highly expressed in normal kidney. It is the aim of the current study to evaluate FXYD2 expression in RCC.
Design: Case records of Barnes Hospital were searched and identified 41 choromophobe RCCs, 38 oncocytomas, 15 clear cell RCCs, and 11 papillary RCCs. Immunohistochemistry for FXYD2, cytokeratin 7 (CK7), and kidney-specific cadherin (KspCdh) was performed along with histochemical analysis for colloidal iron. Fluorescence in situ hybridization (FISH) analysis for chromosomes 1,2,6,10, and 17 was performed on a subset of tumors.
Results: Immunohistochemical staining for FXYD2 showed diffuse, strong immunoreactivity in the basolateral membrane of distal tubules of normal human kidney. 83% (34/41) of chromophobe RCCs were immunoreactive for FXYD2 in a membranous pattern (figure). In contrast, only 8% (3/38) of renal oncocytomas (figure), 11% (2/15) of clear cell RCCs, and 0% (0/11) of papillary RCCs displayed FXYD2 immunoreactivity.
CK7 was immunoreactive in 79% (15/19) of chromophobe RCCs and 39% (7/18) of oncocytomas. KspCdh showed positive staining in 95% (18/19) of chromophobe RCCs and 44% (8/18) of oncocytomas. Colloidal iron stained 79% (15/19) of chromophobe RCCs, and 11% (2/18) of oncocytomas. FISH demonstrated monosomy 1, 2, 6, 10, and 17 in 69% (9/13) of chromophobe RCCs and 11% (2/18) of oncocytomas.
Conclusions: FXYD2, a distal tubule protein, is preferentially expressed in chromophobe RCC. Although both chromophobe RCC and oncocytoma are believed to derive from the distal nephron, they show differential expression of FXYD2, a distal tubule specific protein. This unexpected result highlights subtle differences between these two tumor types. Importantly, FXYD2 may be a diagnostically useful marker to distinguish benign oncocytoma from chromophobe RCC.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 162, Tuesday Morning