Primary explant culture preserves three-dimensional architecture of tumor tissue, intra-tumoral heterogeneity and aspects of tumor microenvironment, including interactions between tumor cells and the adjacent tissue cells. For these reasons, it is believed that the explant cultures capture tumor-specific pathways and their complexities better than possibly any other in vitro or ex vivo tumor model. We are developing a primary human breast tumor explant platform allowing integration of rapid, small-scale genome profiling with validation of tumor specific targets. We show that the explants, processed to 100 uM fragments and cultured on a 3D matrix, contain both epithelial and stromal cells and maintain the viability for up to 12 days. To characterize the explant phenotype and similarity to the original tumor, we have examined explants and the original tumors side-by-side by immunohistochemistry (IHC), immunocytochemistry (ICC) and genome profiling. The biomarkers analyzed by IHC and/or ICC include hormone receptors, cytokines, epithelial and stromal cell markers as well as proliferation and apoptosis markers. A small-scale genome profiling analysis was performed with TruSeq Amplicon Cancer panel. Cancer-related missense mutations were identical in 60% of original tumor/ explant pairs and had minor differences in 40% of original tumor/ explant pairs. Compared to original tumors, proliferation was increased in explants but clear correlation in the level of proliferation between original tumor/ explant was observed. In conclusion, our preliminary findings suggest surprisingly similar genetic landscapes between breast tumor explants and the cognate primary tumors. Therefore, breast tumor explant platforms could predict well the efficacy of molecular targeted and personalized therapies.
Citation Format: Liina Nevalaita, Hanna Ala-Hongisto, Maria Lehtivaara, Päivi Heikkilä, Marjut Leidenius, Panu Kovanen, Outi Monni, Juha Klefström. Primary human breast tumor explant platform for integrated profiling and target validation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1188. doi:10.1158/1538-7445.AM2014-1188