Hedgehog Pathway Expression and Clinical Outcome in Endometrial Carcinoma (EC).
Wadad Mneimneh, Muhammad A Ashraf, Christine E Sheehan, Jeffrey S Ross. Albany Medical College, NY
Background: The expression of hedgehog pathway proteins including including Sonic (Shh) and Desert (Dhh) have been associated with embryonic development and human neoplasia. Hedgehog pathway signaling has not been linked to clinical outcome in EC.
Design: Formalin-fixed, paraffin-embedded tissue sections from 128 endometrial carcinoma, including 104 endometrioid carcinoma (EC), 12 uterine papillary serous carcinoma (PSC) and 12 malignant mesoderm mixed tumor (MMMT), were immunostained by automated methods (Ventana Medical System, Tucson, AZ) using goat polyclonal Shh and Dhh antibodies (Santa Cruz Biotechnology, Santa Cruz, CA). Cytoplasmic immunoreactivity was scored based on staining intensity (weak, moderate, strong) and percentage of positive cells (focal <= 10%, regional 11-50%, diffuse >50%). Results were correlated with clinicopathologic variables.
Results: Immunoreactivity for Shh and Dhh were predominately cytoplasmic. Strong diffuse Shh and Dhh overexpression was observed in 20% and 19% of tumors overall; and 21% and 23% ECs, 17% and 0% PSCs, and 17% and 0% MMMTs, respectively. Shh overexpression correlated with advanced stage (34% advanced vs 15% early, p=0.024) and depth of myometrial invasion (38% invading to more than 50% of the myometrium vs. 17% to less than 50% vs. 0% no invasion, p=0.024). Dhh overexpression also correlated with advanced stage (37% advanced vs 17% early, p=0.033) and depth of myometrial invasion (33% invading to more than 50% of the myometrium vs. 19% to less than 50% vs. 0% no invasion, p=0.04). A significant co-expression was identified between Shh and Dhh (p=0.012). On multivariate analysis, disease recurrence (p=0.004) and advanced stage (p=0.03) independently predict shortened survival.
Conclusions: Overexpression of both Shh and Dhh occurs in EC and is associated with depth of tumor invasion and pathologic stage. Further studies of the hedgehog signaling pathway in EC appears warranted.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 136, Monday Morning