Abstract 3398: High-throughput expression profiling of circulating tumor cells from breast cancer patients as potential therapy decision indicator

Abstract

Abstract Background: The aim of this study was to assess the molecular profiles of circulating tumor cells (CTCs) from metastatic breast cancer (MBC) patients and to evaluate their potential as prognostic and therapy indicators. Methods: Blood samples (5ml) of 77 MBC patients from Czech and German Gynecological Cancer Centers were analyzed for CTCs using the AdnaTest BreastCancer (AdnaGen AG, Germany) for the detection of EpCAM, MUC-1 and HER-2 transcripts. Obtained cDNA molecules have been gene-specifically pre-amplified for multimarker qPCR analysis measured on Biomark® (Fludigm, USA) microfluidic chip for 48 samples and 48 testing positions (in total: 2304 rxn, 31 tumor specific-genes, 30 MBC samples, respectively). qPCR- results have been analyzed by GENEX v.s. 5.0 software (MultiD, SE). Results: CTCs were found in 42% of the MBC patients. Based on the AdnaTest, two distinct groups of CTC positive-MBC patients have been identified after principal component analysis of the gene expression data. The first CTC-positive group had relatively high EPCAM, MUC1, KRT19, HER2, AURKA, and MCM expression. In contrast, expression of PTEN, SATB1 and CD45 was low. The second CTC-positive group showed lower expressions of AURKA, EPCAM, and KRT19 than the first group. Furthermore, markers typically expressed in CD45 positive cells like SATB1, AKT, PARP, PTEN, mTOR, but also oncogene MYC and tumor suppressor TP53 were highly expressed in this group. The samples of CTC-negative MBC patients were characterized by low expression of the cancer phenotype associated genes EPCAM, KRT19, and MUC1, but showed comparably higher expression of genes associated with a stem cell like phenotype such as TWIST, ALDH1 and CD24. Conclusions: Based on our data, we conclude that CTCs enriched by the AdnaGen-technology are heterogeneous and do not necessarily express EPCAM. Even CTCs with low EPCAM expression but with elevated KRT19 and AURKA levels may represent a subgroup of high risk metastatic BC patients. Follow-up of the patients will show whether specific gene profiles of CTCs will a) identify responders and non-responders to breast cancer related therapies and b) be useful for personalized therapy of MBC in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3398. doi:1538-7445.AM2012-3398