BCA2 Is Differentially Expressed in Renal Oncocytoma: An Analysis of 158 Renal Neoplasms
Laleh Ehsani, Arun Seth, Adeboye O Osunkoya. Emory University School of Medicine, Atlanta; Sunnybrook Health Sciences Center, Toronto, Canada
Background: The distinction between renal oncocytoma and renal cell carcinoma, especially chromophobe renal cell carcinoma and clear cell carcinoma with oncocytic features is important due to the different biologic potentials of these tumors. RING E3 ligases have now become the subject of intense studies for their roles in disease and as potential therapeutic targets. All RING E3 ligases, including BCA2, contain a consensus protein sequence that would complex two or more zinc ions in the expressed protein. Identification of which ubiquitin ligases specifically affect distinct cellular processes is essential to the development of targeted therapeutics in these tumors. The ubiquitin-proteasome system regulates the turnover of proteins that have essential roles in the cell cycle, apoptosis, DNA damage repair, and in protein trafficking, which makes this pathway a target for oncogenic events. In this study we investigated expression of BCA2 in renal oncocytoma and renal cell carcinoma.
Design: Tissue microarrays (TMAs) were constructed from 158 patients with clear cell renal cell carcinoma, chromophobe renal cell carcinoma, papillary renal cell carcinoma, oncocytoma and oncocytic neoplasm, favor oncocytoma. The latter tumors were cases provisionally signed out as such by consulting general pathologists, and were morphologically consistent with renal oncocytoma, but invaded perinephric adipose tissue. Immunohistochemical stains for BCA2 were performed on the TMAs.
Results: The tumors were composed of 114/158 (72%) cases renal cell carcinoma, in which 104/114 (91%) were clear cell renal cell carcinoma, 8/114 (7%) were chromophobe renal cell carcinoma and 2/114 (2%) were papillary renal cell carcinoma. 38/158 (24%) cases were renal oncocytoma and 6/158 (4%) were cases provisionally signed out by consult contributors as oncocytic neoplasm, favor oncocytoma. 114/158 (100%) cases of renal cell carcinoma were negative for BCA2. 38/38 (100%) cases of renal oncocytoma were positive for BCA2. 6/6 (100%) of cases designated as oncocytic neoplasm, favor oncocytoma were also positive for BCA2.
Conclusions: This is the first study to date evaluating the expression of BCA2 in renal neoplasms. BCA2 is differentially expressed in renal oncocytoma, including those with locally invasive potential. BCA2 is a marker that may be utilized in the distinction between renal oncocytoma and its mimickers, and may also be a potential therapeutic target in patients with large renal oncocytomas, who are not good surgical candidates.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 129, Monday Morning