Smooth Muscle Component of Renal Angiomyolipoma Is Polysomic for Chromosome 7
O Chang, S Madugula, L Deane, E Wiley, G Chappell, V Lindgren, S Setty. University of Illinois at Chicago, Chicago, IL
Background: Renal angiomyolipoma (AML) is a rare neoplasm in the PEComa family with a triphasic cell population composed of smooth muscle (SM), fat (F), and vessels (V) in varying proportions. Larger tumors carry the potential for rapid and massive hemorrhage, and current management relies on radiographic tumor size (≥4cm necessitating intervention). The cell of origin and factors influencing progression of tumor growth remain unclear. We investigated molecular cytogenetic and immunohistochemical (IHC) properties of renal AML to gain insight on the development, and potential prognostic features of this neoplasm.
Design: Formalin-fixed, paraffin-embedded tumors resected from 11 subjects (10 female, 1 male with tuberous sclerosis) between 2004-2009, were obtained from UICMC archives. A tissue microarray consisting of 2mm cores was constructed by sampling the three histologic elements and IHC for HMB45 (Dako)and EGFR (Ventana) was performed. Scoring was based on percentage and intensity of reactivity, ranging from 0-3+. 4 µm sections were processed for dual-color interphase fluorescence in situ hybridization (FISH) using a centromeric probe for chromosome 7 and an EGFR locus specific probe (7p12, Abbott Molecular). Regions of SM, F, and V were scored for EGFR copy-number (n=40 cells per tumor). Protein expression and copy-number were correlated with tumor size (<4cm versus ≥4cm).
Results: Polysomy of chromosome 7 was identified in 10 of 11 cases, confined to the SM cell population. Copy-number of the EGFR gene was significantly higher for SM versus F (p<0.001) and V (p<0.001) of the tumors. Tumors ≥4cm exhibited higher copy-number compared to those <4cm (p=0.010). EGFR gene amplification was absent in all tumors. 10 of 11 cases (91%) were positive for EGFR IHC without a difference in expression between tumors <4cm and those ≥4cm. While all 11 tumors had at least focal positivity for HMB45, stronger staining was seen in the SM component of tumors ≥4cm (p=0.037).
Conclusions: Our data suggests that polysomy of chromosome 7 characterizes the smooth muscle component of renal AML and this abnormality is not present in the tumor fat and vessel components. This may suggest divergence of the smooth muscle tumor clone from the vessel component during development. The high EGFR copy-number and stronger HMB45 expression in larger tumors, also favors tumor progression and supports the possibility of targeted therapy.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 85, Wednesday Morning