Gene Expression Profiling of Clear Cell Papillary Renal Cell Carcinoma
Kevin E Fisher, Qiqin Yin-Goen, Dianne Alexis, Joseph S Sirintrapun, William Harrison, Benjamin R Isett, Michael R Rossi, Carlos S Moreno, Andrew N Young, Adeboye O Osunkoya. Emory University School of Medicine, Atlanta; Wake Forest University School of Medicine, Winston-Salem
Background: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described distinct variant of renal cell carcinoma (RCC) that shares some overlapping histologic and immunohistochemical features of clear cell RCC (CCRCC) and papillary RCC (PRCC). Our previous work elucidated differential molecular expression biomarkers that distinguish CCRCC (carbonic anhydrase IX [CA9]) from PRCC (schwannomin-interacting protein 1 [SCHIP1]) and α-methylacyl coenzyme-A racemase [AMACR]). Although the immunohistochemical profile of CCPRCC is well described, the mRNA expression profile of CCPRCC has not been well characterized in multiple series. Using a select subset of previously identified candidate genes, we investigated the gene expression profile of CCPRCC.
Design: 12 cases of CCPRCC with classic histologic and immunohistochemical profile were selected for molecular analysis after histologic review by the senior author. RNA was extracted from formalin-fixed paraffin-embedded tissue and cDNA was prepared. Quantitative PCR was performed in triplicate, targeting CA9 (Hs00154208_m1), AMACR (Hs01091292_m1), and SCHIP1 (Hs00205829_m1). 28S ribosomal RNA was used as an amplification control (RNA28S1, Hs03654441_s1).
Results: Successful cDNA amplification occurred in the 12 cases of CCPRCC. SCHIP1 was successfully amplified in 1/12 cases (8.3%), CA9 in 9/12 cases (75%), and AMACR in 6/12 cases (50%). Three cases of CCPRCC coexpressed both CA9 and AMACR mRNA, and one case coexpressed CA9, AMACR, and SCHIP1 mRNA. CCPRCCs expressed approximately 60 to 1000-fold more CA9 mRNA compared to AMACR mRNA (Comparative ΔΔCt values ranging between -5.979 and -9.896).
Conclusions: Variable expression of CA9, AMACR, and SCHIP1 mRNA in CCPRCC confirms that though these tumors are distinct from CCRCC and PRCC, they share some molecular expression profiles of both CCRCC and PRCC. The increased expression of CA9 mRNA relative to AMACR mRNA, suggests that the clear cell molecular phenotype is likely more dominant in a subset of patients with CCPRCC. SCHIP1 mRNA which is typically increased in PRCC was also not amplified in the vast majority of cases. Amplification optimization and investigation of additional candidate genes is ongoing. Understanding the molecular basis of CCPRCC will assist in future sub-classifications and molecular-targeted treatment of patients with this unique tumor.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 98, Wednesday Morning