GADD45a Protein Expression in Endometrial and Ovarian Tumors
EA Slodkowsak, J Torres-Mora, CE Sheehan, JS Ross. Albany Medical College, Albany, NY
Background: GADD45a (growth arrest and DNA-damage-inducible 45 alpha) expression is increased by growth arrest conditions and exposure to DNA-damaging agents mediated by the activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The prognostic significance of GADD45a expression in endometrial and ovarian epithelial tumors has not been previously studied.
Design: Formalin-fixed paraffin-embedded tissue sections from 82 endometrioid carcinomas (EC), 17 uterine papillary serous carcinomas (PSC) and 80 primary ovarian epithelial tumors including benign tumors (BN), tumors of low malignant potential (LMP), and primary ovarian carcinomas (OC) were immunostained by an automated method (Ventana Medical Systems Inc., Tucson, AZ) using rabbit polyclonal GADD45a antibody (sc-792; Santa Cruz Biotechnology, Santa Cruz, CA). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Overexpression of GADD45a was observed in 49% EC and 59% PSC and showed an overall trend for high expression in early stage tumors (55% early vs. 33% advanced stage, p=0.08). Within the endometrioid carcinoma subtype, GADD45a overexpression was higher in early stage tumors (54% early vs. 23% advanced stage, p=0.038) and correlated with the depth of myometrial invasion (p=0.039). GADD45a overexpression was noted in 29% BN, 20% tumors of LMP, and 46% OC. A trend for a higher expression rate in OC versus BN and LMP was noted, but did not reach statistical significance (p=0.09). In BN, LMP and OC, 0% mucinous tumors overexpressed GADD45a, compared to 60% clear cell, 48% papillary serous and 25% endometrioid tumors (p=0.04). GADD45a expression did not correlate with tumor grade, stage or survival in either EC or OC.
Conclusions: GADD45a overexpression correlates with tumor stage and the depth of myometrial invasion in EC, subtypes of ovarian carcinoma and trends toward an association with invasive versus benign or borderline status in ovarian epithelial tumors. Further study of GADD45a expression in gynecologic malignancies appears warranted.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 161, Wednesday Afternoon