Sonic Hedgehog (Shh) and Patched-1 (PTCH1) Protein Expression in Invasive Mammary Carcinoma; (PTCH1) Protein Expression Independently Predicts Outcome
Jennifer Garbaini, Kelly-Ann Kim, Christine Sheehan, Ann Boguniewicz, Jeffrey Ross. Albany Medical College, Albany, NY
Background: Shh signaling regulates PTCH1 expression in the organization of embryonic development and may play a critical role in mammary gland morphogenesis and cancer development. Aberrant expression of Shh and PTCH1 result in abnormal growth of mammary ducts, but have not been linked to clinical outcome in invasive mammary cancer.
Design: Formalin-fixed, paraffin-embedded tissue sections of 175 invasive mammary carcinomas, including 125 ductal carcinomas (IDC) and 50 lobular carcinomas (ILC), were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using goat polyclonal Shh (sc-1194) and rabbit polyclonal PTCH1 (sc-9016) (Santa Cruz Biotech, Santa Cruz, CA) antibodies. Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Cytoplasmic Shh overexpression was observed in 94/175 (54%) of invasive carcinomas. Shh overexpression correlated with high tumor grade [70% grade III vs 45% grade II vs 48% grade I, p=0.035], advanced stage (65% advanced vs 46% early, p=0.02), positive lymph node status (60% node positive vs 44% node negative, p=0.047), and disease recurrence (67% recurrent vs 50% non-recurrent, p=0.045). Cytoplasmic PTCH1 overexpression was observed in 138/175 (79%) of invasive carcinomas. PTCH1 overexpression correlated with high tumor grade [95% grade III vs 76% grade II vs 78% grade I, p=0.033] and disease free survival (90% recurrent vs 75% non-recurrent, p=0.036). On multivariate analysis, advanced stage (p=0.000), ER negative status (p=0.004), and PTCH1 overexpression (p=0.021) were independent predictors of disease–free survival; while advanced stage was an independent predictor of overall survival (p<0.0001).
Conclusions: Shh and PTCH1 expression are associated with adverse clinicopathologic parameters in invasive mammary cancer with PTCH1 expression found to be an independent predictor of disease-free survival. Further study of the hedgehog pathway in breast cancer appears warranted.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 53, Wednesday Morning