Oncocytic Renal Neoplasms (ORN): An Immunohistochemical (IHC) Study with an Emphasis on Mammalian Target of Rapamycin (mTOR) Related Proteins
SM Rohan, ME Dudas, A Gopalan, SW Fine, VE Reuter, SK Tickoo. Memorial Sloan Kettering Cancer Center, NY, NY
Background: Many patients with the Birt-Hogg-Dub (BHD) syndrome develop renal neoplasms. Tumors with oncocytic features are over-represented in this setting. The mTOR pathway plays an important role in a subset of renal tumors. Recently, alterations of the BHD gene have been shown in various types of sporadic renal tumors and the protein product of the gene has been shown to interact with the mTOR pathway, resulting in overexpression of mTOR related proteins. In this study we evaluated the IHC expression of several markersincluding mTOR related proteins (p-AKT, p-S6, p-4EBP1)in a cohort of sporadic ORN.
Design: 54 cases of ORN, including 9 oncocytoma (RO), 26 chromophobe carcinoma (CHR) and 19 renal cell carcinoma, unclassified, low grade oncocytic type (ORNU). were examined The unclassified category included tumors with morphologic features that precluded their inclusion among RO or CHR. IHC was performed for CK7, CD117, carbonic anhydrase IX (CA9), TFE3, p-AKT, p-S6 and p-4EBP1. Staining was graded as absent/weak (0 or 1+, 0-25% cells positive) or strong (2+ or 3+, 26 - 100%). Cytoplasmic / membranous expression of CD117, CK7, CA9, and p-S6 were considered positive. Only nuclear expression of TFE3, p-AKT and p-4EBP1 were considered positive.
Staining Grade (%) by tumor type
|CHR (n=26)||RO (n=9)||ORNU (n=19)|
|CD117||4 (15)||22 (85)||1 (11)||8 (89)||4 (21)||15 (79)|
|CK7||8 (31)||18 (69)||9 (100)||-||19 (100)||-|
|p-AKT||16 (62)||10 (38)||5 (56)||4 (44)||12 (63)||7 (37)|
|p-4EBP1||26 (100)||-||6 (66)||3 (34)||16 (85)||3 (15)|
|p-S6||25 (96)||1 (4)||9 (100)||-||16 (85)||3 (15)|
No RO or ORNU expressed CK7. None of the tumors studied expressed CA9 or TFE3. Of the mTOR related markers, p-AKT expression was observed most often, with strong expression in 37 to 44% of cases. Expression of p-4EBP1 was seen in RO (34%) and ORNU (15%) but not in CHR.
Conclusions: Most tumors studied expressed CD117 irrespective of histological classification. CK7 was strongly expressed in most cases of CHR, but none of the RO or ORNU. Strong expression of p-4EBP1 was only seen in RO and ORNU. Over one third of all ORN in this study express p-AKT. The staining patterns suggest that ORNU are more closely related to RO than CHR. Correlation of these IHC results with alterations in the BHD gene may provided a mechanistic explanation for mTOR related marker expression in these tumors.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:00 PM
Poster Session II # 117, Monday Afternoon