Expression of Beclin-1 Protein in Breast Cancer
Ankit V Gandhi, Phoebe J Holmes, Juan P Palazzo. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Autophagy is the self-digestion of intracellular organelles in cells that undergo stress. Beclin-1, the mammalian orthologue of Atg6 (autophagy-related gene), is fundamental to the formation of the autophagosome involved in this process. The end result is either adaptation or cell death, which may explain how both increased and decreased beclin-1 levels are linked to different types of cancer. In regards to breast cancer, beclin-1 may be of prognostic value if its role is fully elucidated. In this study, the staining of beclin-1 in benign breast tissue, ductal carcinoma in situ (DCIS), low-grade carcinoma, and high-grade carcinoma was evaluated to determine the correlation between beclin-1 and cancer progression.
Design: We studied 521 patients who underwent surgery from 1999-2008 at TJUH. There were 113 cases of benign breast tissue, 47 cases of DCIS, 170 cases of low-grade carcinoma, and 191 cases of high-grade carcinoma. All cases were stained for Beclin-1 (1:200, EPR1733Y, Epitomics, Burlingame, CA) with appropriate controls. Cytoplasmic staining was considered positive and cases were categorized by intensity (weak, moderate, strong). The study was approved by the IRB.
Results: Benign breast, DCIS, and low-grade cases demonstrated moderate-strong cytoplasmic staining of beclin-1 in 95/113 (84%), 38/47 (81%), and 131/170 (77%) of cases, respectively. However, only 38/191 (20%) of the high-grade cases showed moderate-strong staining, the majority (70%) being negative.
Conclusions: Beclin-1 staining was increased in cases of benign tissue, DCIS, and low-grade carcinoma in contrast to decreased or negative staining in cases of high-grade carcinoma. These findings indicate that beclin-1 inversely correlates with histological grade and progression to high-grade cancer. Stress-induced inhibition of autophagy may propagate breast malignancy by reducing cell death. Thus, our results suggest that beclin-1 could be used as a valuable marker in human breast cancer.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 9, Wednesday Afternoon