Subcellular Localization of Lipocalin-2/NGAL Correlates with Histologic Type and Grade of Renal Cell Carcinomas (RCC)
JA Levesque, JS Ross, CE Sheehan, A Hayner-Buchan. Albany Medical College, Albany, NY
Background: Lipocalins are a small family of secreted proteins involved in cell regulation,proliferation and differentiation. Lipocalin-2, also known as neutrophil gelatinase-associated lipocalin, is expressed in the nucleus, cytoplasm and cytoplasmic membrane in both normal and neoplastic human tissues and is upregulated in several malignancies including esophageal, rectal and breast carcinomas. The current study was done to characterize NGAL expression in renal cell carcinoma (RCC).
Design: Formalin-fixed, paraffin-embedded tissue sections from 73 renal cell carcinomas (62 clear cell carcinomas and 11 other subtypes – including 6 papillary, 3 chromophobe, and 2 sarcoma) were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using rat monoclonal lipocalin-2/NGAL (R&D Systems, Minneapolis, MN). 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: Cytoplasmic lipocalin-2 overexpression was observed in 20/73 (27%) tumors; and correlated with tumor type [55% other subtypes vs 23% clear cell, p=0.028], high tumor grade (p=0.002), and tumor stage (p=0.041); while showing a trend toward correlation with survival of less than 5 years (p=0.12). Membranous overexpression was observed in 21/73 (29%) tumors; and correlated with tumor type [34% clear cell vs 0% other subtypes, p=0.022] and low tumor grade (p=0.032). Nuclear lipocalin-2 expression was noted in 14/73 (19%) tumors and correlated with lengthened survival (p=0.02) and showed a trend toward correlation with low tumor grade (p=0.10). There was an inverse correlation between cytoplasmic and membranous immunoreactivity (90% of tumors overexpressing cytoplasmic lipocalin-2 protein lacked membranous overexpression vs 10% expressing both patterns, p=0.03). On multivariate analysis, advanced tumor stage and disease recurrence independently predicted survival.
Conclusions: The association of cytoplasmic lipocalin-2 expression with non-clear cell histology and high tumor grade, membranous lipocalin-2 expression with clear cell histology and low tumor grade and nuclear lipocalin-2 expression with lengthened survival and low tumor grade supports a role for lipocalin-2 in the biology of RCC.In addition, the prognostic significance of lipocalin-2 expression in RCC warrants further study.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 107, Wednesday Morning