Patched-1 (PTCH1) Hedgehog Pathway Protein Expression and Clinical Outcome in Diffuse Large B-Cell Lymphoma (DLBCL).
Megan C Davies, Li Li, Christine Sheehan, Tipu Nazeer. Albany Medical College, NY
Background: Activation of the hedgehog signaling pathway is implicated in embryonic development as well as the differentiation, proliferation, and maintenance of multiple adult tissues. Aberrant expression Patched-1 has been linked to neoplastic transformation, but has not been related to clinical outcome in DLBCL.
Design: Formalin-fixed, paraffin-embedded sections from 83 DLBCLs were immunostained by automated methods (Ventana Medical Systems, Inc., Tucson, AZ) using rabbit polyclonal patched antibody (clone H-267, Santa Cruz Biotechnology, Santa Cruz, CA). Cytoplasmic and nuclear immunoreactivity was assessed in all cases and semiquantitatively scored based on staining intensity (weak, moderate, strong) and distribution (focal <= 10%, regional 11-50%, diffuse >50%). The results were then correlated with clinicopathologic variables.
Results: Immunoreactivity was predominantly cytoplasmic for patched protein, while nuclear immunoreactivity was also observed in a small subset of cases. Intense diffuse cytoplasmic expression was noted in 43% of cases. Cytoplasmic patched overexpression correlated with advanced tumor stage [54% advanced stage versus 28% early stage, p=0.049] and extranodal involvement [62% extranodal versus 31% nodal, p=0.005]. On multivariate analysis, only advanced tumor stage independently predicted shortened survival.
Conclusions: Patched-1 protein pathway expression is associated with clinical outcome variables in DLBCL. Ptch-1 overexpression was associated with advanced tumor stage and extranodal involvement. Cases of DLBCL with overexpression of Ptch1 show advanced tumor stage which is an independent predictor of shortened patient survival.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 209, Wednesday Afternoon