Abstract 35: A universal marker for the detection of epithelial-mesenchymal transitioned circulating tumor cells and their prognostic relevance in epithelial cancers

Abstract

Abstract Circulating tumor cells (CTCs) are the tumor cells shed from the primary tumor tissues into the bloodstream or lymphatic vessels. These CTCs are considered to be emerging tools for the detection and prognosis of several types of metastatic cancers. At present, CTC markers are limited to epithelial cancers and there are no specific markers available to detect mesenchymal and epithelial-mesenchymal transformed (EMT) CTCs. EMT cells are characterized by increased motility and invasiveness and are known to escape detection technologies that use EpCAM and cytokeratins as CTC markers. We have previously reported the detection of mesenchymal cancer cells from blood of sarcoma cancer patients for the first time using a novel monoclonal antibody 84-1. Here we report the detection of EMT CTCs from colon, breast and prostate cancer patients using 84-1 monoclonal antibody. Isolated EMT CTCs were characterized for EMT phenotype by staining for Snail, Slug, Twist-1 and FOXC2. To analyze the efficiency of CTC detection, we compared the CTC counts obtained using 84-1 antibody to that of the FDA approved CellSearch method. We collected blood samples from breast and prostate cancer patients and isolated a) EMT CTCs using 84-1 and b) Epithelial CTCs using Cell Search. For validation purposes, we analyzed an experimental set of patient samples that included normal, non-metastatic and metastatic samples to derive a threshold of detecting CTCs in these patients. After validating a threshold value of the CTC, we used an experimental set that was randomized to evaluate CTCs from different patient sets. Since the experimental set consisted of randomized set of patients with different stages of disease progression and treatments, we evaluated the association between CTC count and therapeutic outcome (progression/ stable & responding). Our results indicated that patients with ≥ 5 EMT CTCs/7.5 mL as detected by 84-1 antibody were independent predictors of therapeutic outcome in breast and prostate cancer patients. Detection using 84-1antibody was much more sensitive and specific when compared with CellSearch method. Collectively, our observations provide a novel technology to selectively detect and isolate EMT CTCs. Detection and molecular characterization of CTCs is one of the fastest growing areas of translational cancer research. Utilizing 84-1, we can enumerate and isolate rare EMT CTCs that will aid as prognostic indicators of therapeutic outcome, metastasis, and relapse and will contribute to the development of specific targeted therapies, an ultimate goal of personalized medicine. Citation Format: Arun Satelli, Zachary Brownlee, Scott Kopetz, Michael Overman, Qing H. Meng, Shulin Li. A universal marker for the detection of epithelial-mesenchymal transitioned circulating tumor cells and their prognostic relevance in epithelial cancers. [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 35. doi:10.1158/1538-7445.AM2014-35