High Levels of Expression of Activating Transcription Factor-2 (ATF2) Are Associated with High-Grade Pancreatic Intraepithelial Neoplasia and Pancreatic Ductal Adenocarcinoma
JJ Liang, S Zhu, W Li, R Bruggeman, B Han. Penn State Milton S Hershey Medical Center, Hershey, PA; University of Texas Health Science Center at Houston, Houston, TX
Background: Activating transcription factor-2 (ATF2, or CREB2) is a sequence-specific DNA-binding protein that belongs to the bZIP family, a key factor in p38/C-Jun N-terminal kinase signaling passway. ATF2 overexpression has been detected in various tumors, including melanoma, ovary and breast caners. The expression and significance of ATF2 in human pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDA) have not been studied in detail. In this study, we examined expression of ATF-2 in human PanIN lesions and PDA.
Design: We prepared a tissue microarray consisting of duplicated 2.0-mm cores of PDAs (n=38), PanIN I (n=16), PanIN II (n=8) and PanIN III (n=6) lesions and non-neoplastic pancreatic tissues (n=22). Nuclear expression of ATF-2 was evaluated by immunohistochemistry with rabbit anti-human ATF-2 (N-96) polyclonal antibodies (1:500, Santa Cruz Biotechnology Inc). Immunoreactivity was scored based on the sum of staining intensity (0 = none, 1 = mild, 2 =moderate, 3 = marked) and percentage of cells staining (0 = <1%, 1 = 2∼10%, 2 =11∼40%, 3 = >40%) (Potential range of 0 to 6). Statistics was performed by Student's t test.
Results: There was significantly higher expression of ATF-2 in PDAs (mean 4.2+0.8) and PanIN III (mean 3.8 +0.7), compared to PanIN II (mean 2.4 +0.5), PanIN I (mean 2.1 +0.4), and normal bile ductal epithelium (mean 1.8 +0.5) (p<0.01). However, there is no significant difference in ATF-2 expression between normal bile ductal epithelium and either PanIN I or PanIN II lesions (p>0.05).
Conclusions: High levels of expression of ATF-2 are associated with high-grade PanIN lesion and PDAs. Our results suggest that activation of ATF-2 gene involve the progression of later stage PanIN to PDAs.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 209, Tuesday Afternoon