Decreased BRG1 Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma, a Potential Role for a Tumor Suprressor Gene Inactivation in Oncogenesis
Enrico Munari, Alcides Chaux, Sheila F Faraj, Nilda D Gonzalez Roibon, Rajni Sharma, George J Netto. Johns Hopkins Hospital, Baltimore, MD; Universidad del Norte School of Medicine, Asuncion, Paraguay
Background: BRG1/SMARCA4, a member of the SWI/SNF complex, is involved in ATP-dependent chromatin remodeling processes that are critical for cellular differentiation, DNA repair and proliferation. Several studies have demonstrated a tumor suppressor role for BRG1 in different types of cancer. Moreover, BRG1 is a direct target of microRNA-21 that is upregulated in a variety of malignancies including renal cell carcinoma, suggesting a potential role in oncogenesis of renal tumors. To our knowledge, BRG1 expression has not been studied in clear cell renal cell carcinoma (ccRCC). Our aim was to evaluate BRG1 expression in primary and metastatic ccRCC and to determine its potential role as a prognosticator.
Design: 68 primary ccRCC and 41 unrelated metastatic ccRCC were used to build 3 tissue microarrays (TMA) with triplicate spots per case. Additionally, paired non-neoplastic kidney tissue was included in all primary cases. BRG1 expression was evaluated by immunohistochemistry. An H score representing the sum of staining intensity (0-3) X extent (0-100) was calculated in each spot. The median H score per case was used for statistical analyses. Follow-up data was available in 48/68 primary ccRCC patients and in all 41 patients with metastatic ccRCC. Median follow-up was 33.5 months (range: 2 to 231 months). Outcome endpoints of the study included overall survival, cancer-specific survival, and tumor progression.
Results: BRG1 expression was significantly decreased in primary and metastatic ccRCC compared to normal kidney (P=0.0001). BRG1 expression was similar in primary and metastatic ccRCC (P=0.70). Using Cox proportional hazards regression, BRG1 expression was not associated with overall survival (HR=1.001, P=0.68), cancer-specific survival (HR=0.99, P=0.72), or tumor progression (HR=0.99, P=0.81).
Conclusions: Our finding of decreased BRG1 expression in primary and metastatic ccRCC compared to paired non-neoplastic renal tissue, points to a potential role for BRG1 tumor suprressor gene inactivation in ccRCC oncogenesis. The findings merit further investigation. BRG1 expression failed to predict outcome in our cohort of ccRCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 132, Wednesday Morning