Abstract 2497: Upregulation of annexin A8 is a common molecular phenotype of aberrant breast acinar morphogenesis induced by different genetic factors.

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Abstract It is estimated that up to 90% of women have benign breast lesions, some of which are pre-malignant. In situ lesions, particularly the ones that involve the ducts (ductal carcinoma in situ, DCIS), have the potential to progress into invasive malignant lesions and become life threatening. These breast premalignant states are identified because of specific morphological tissue abnormalities. Three-dimensional (3D) cultures of human mammary epithelial cells closely recapitulate breast acinar morphogenesis. While untransformed mammary epithelial cells form hollow acini, lined by polarized, non-proliferating cells, breast cancer cells form acini filled with non-polarized, actively proliferating cells, similar to DCIS. By using a proteomic approach in a panel of morphologically aberrant acini derived from human breast epithelial cells, we found that the disruption of acinar morphogenesis by different genetic factors generates a common proteomic signature. Among the proteins that we found consistently upregulated, we identified Annexin A8 (ANXA8), a member of the annexin family of calcium and membrane-binding proteins with a wide range of cellular functions, including cell division, apoptosis, and cell growth regulation. We tested ANXA8 expression in tissue samples from patients with atypical ductal hyperplasia (ADH), and tissue microarrays of DCIS, with or without, history of invasive breast cancer. Interestingly, this analysis detected ANXA8 increased expression in atypical proliferating ducts relative to non-proliferative ducts, making ANXA8 a potential marker of breast pre-malignancies. Acknowledgments: this study was funded by grants of the Susan Komen Foundation, the Breast Cancer Coalition of Rochester, the Friends for an Earlier Test of Breast Cancer Foundation. Citation Format: Stefano Rossetti, Francesca Corlazzoli, Nicoletta Sacchi. Upregulation of annexin A8 is a common molecular phenotype of aberrant breast acinar morphogenesis induced by different genetic factors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2497. doi:10.1158/1538-7445.AM2013-2497 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.