Desert Hedgehog (DHH) and Sonic Hedgehog (SHH) Overexpression in Colorectal Cancer (CRC): Correlation with AJCC Stage and Overall Survival.
Erin Flynn, Karl Robstad, Muhammad A Ashraf, Christine E Sheehan, David M Jones, Jeffrey S Ross. Albany Medical College, NY
Background: The Hedgehog signaling pathway has been associated with embryonic development and neoplasia. The prognostic significance of Shh and Dhh expression in CRC has not been widely studied.
Design: Formalin-fixed, paraffin embedded sections from 155 colorectal adenocarcinomas (CRCs) were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) with goat polyclonal Dhh and Shh antibodies (Santa Cruz Biotechnology, Inc, Santa Cruz, CA). Cytoplasmic immunoreactivity of each protein was semiquantitatively assessed in the tumor for all cases. Scoring was based on staining intensity and distribution and results were correlated with clinicopathologic variables.
Results: Moderate to marked, diffuse Dhh overexpression was noted in 83% tumors and correlated with advanced AJCC stage (90% of stage III/IV and 76% stage I/II; p=0.024), positive lymph node status (92% of node positive and 70% of node negative, p<0.0001), and shortened overall survival (88% in those expired and 69% in those alive; p=0.004). Intense diffuse Shh overexpression was noted in 28% tumors and correlated with early AJCC stage (39% of stage I/II and 14% stage III/IV; p<0.0001); and negative lymph node status (43% of node negative and 14% of node positive, p<0.0001). There was significant coexpression of both proteins (p=0.049). On multivariate analysis, pathologic stage (p<0.0001) and Dhh overexpression (p=0.031) were independent predictors of overall survival.
Conclusions: Shh and Dhh are frequently coexpressed in CRC, with Dhh overexpression more directly associated with advanced AJCC stage and positive lymph node status compared to Shh overexpression. The finding that Dhh overexpression was an independent predictor of overall survival further supports the clinical development of Hedgehog pathway inhibitors for the treatment of CRC.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 88, Monday Morning