ALDH1 Expression Is Associated with Low Tumor Grade and Stage in Renal Cell Carcinomas (RCC).
Jessica A Levesque, Jeffrey S Ross, Christine E Sheehan, Ronald P Kaufman, Alida Hayner-Buchan. Albany Medical College, NY
Background: ALDH1 is a member of the aldehyde dehydrogenase family that plays a major role in the biosynthesis of retinoic acid, a regulator of cellular proliferation, differentiation and survival. ALDH1 is overexpressed in many head and neck squamous cell carcinomas, predicts poor clinical outcome in breast cancer and correlates with a favorable prognosis in ovarian cancers. This study examines ALDH expression in renal cell carcinoma (RCC).
Design: Formalin-fixed, paraffin-embedded tissue sections from 74 renal cell carcinomas were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using mouse monoclonal ALDH1 (clone 44/ALDH; BD Biosciences). Cytoplasmic, membranous, and nuclear immunoreactivity were semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Membranous ALDH1 overexpression was observed in 55/74 (74%) RCC; and correlated with tumor type [79% clear cell vs 45% other subtypes, p=0.018] and low tumor grade [82% low grade vs 58% high grade, p=0.029]. Cytoplasmic ALDH1 overexpression was observed in 38/74 (51%) tumors; and correlated with early stage [60% early stage vs 35% advanced stage, p=0.040]. Nuclear ALDH1 overexpression was noted in 31/74 (42%) RCC and showed a trend toward correlation with low tumor grade [48% low grade vs 28% high grade, p=0.094]. There was correlation between nuclear and membranous immunoreactivity (90% of RCC overexpressing nuclear ALDH1 protein also exhibited a membranous pattern of overexpression, p=0.007). On multivariate analysis, advanced tumor stage and disease recurrence independently predicted survival.
Conclusions: ALDH1 overexpression in renal cell carcinoma correlates with low tumor grade (membranous and nuclear staining) and early pathologic stage (cytoplasmic staining). ALDH1 expression may exert a favorable impact in renal cell carcinomas.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 109, Wednesday Morning