Abstract 387: Non small cell lung cancer and circulating tumor cell: A different expression of EpCam and cytokeratins
Authors: Rossi Elisabetta , Manicone Mariangela , Facchinetti Antonella , Aieta Michele , De Faveri Stefania , Scaini Maria Chiara , Possidente Luciana , Terstappen Leon W.M.M. , Zamarchi Rita 
Published: August 2015

Abstract
Non-small cell lung carcinoma (NSCLC) is a major cause of cancer-related death in both men and women globally (http://www.cancer.org/cancer/lungcancer-nonsmallcell/detailedguide/nonsmall-cell-lung-cancer-key-statistics), (Ferlay, Steliarova-Foucher et al. 2013). Despite recent advances in early tumor detection, surgical treatment, radio-chemotherapy, and targeted therapy, the NSCLC-related high mortality rate remains a daunting challenge (Jemal, Bray et al. 2011). Although targeted therapy, especially against epidermal growth factor receptor (EGFR), has greatly advanced, only 15% of NSCLC patients experience therapeutic benefits (Keedy, Temin et al. 2011).
Since predictive biomarkers are lacking so far, Circulating Tumor Cell (CTC) assays have gained interest to assist clinicians in patient management.
In NSCLC, CTCs show a slightly different cytokeratin (CK) pattern and a lower expression of full-length Epithelial Cell Adhesion Molecule (EpCAM) compared to other carcinomas (Fong, Seeber et al. 2014). Indeed, 80% of patients were CTC-positive by the EpCAM-independent ISET compared to only 23% by standard CellSearch assay (Krebs, Sloane et al. 2011).
We questioned whether we could detect a higher number of CTCs by implementing the standard CellSearch assay with an expanded CK pattern, and by using an Autoprep Sample Collection Device (ASCD), designed in the 7PQ CTCtrap project, to collect cells actually discarded by the CellSearch platform (EpCAM low/negative cells).
Methods: We evaluated 65 patients at baseline; 2 blood draws were collected and analyzed by the standard and the implemented (including CK: 5, 6, 7, 14, 17) CTC assays. In three cases, we evaluated CTCs by using ASDC in conjunction with CellSearch platform.
Results: At baseline, CTCs as detected with expanded CK panel were associated with a poorer prognosis. Indeed, CTC-positive patients had a significant lower median PFS (108 days) than CTC-negative patients (254 days; Kaplan-Meyer, Log-Rank test p = 0.017). Furthermore, by ASDC we were able to detected EpCAM low/negative epithelial cells, as confirmed by CK expression. Curiously, we observed an inverse association between the number of CTCs as detected by CellSearch assay and the one in ASDC fraction.
Conclusions: The expanded CK panel improves CTC detection and potentially discloses a more aggressive disease. Accrual is ongoing; further analysis will investigate the prognostic impact of EpCAM low/negative epithelial cells on NSCLC patients.
Citation Format: Elisabetta Rossi, Mariangela Manicone, Antonella Facchinetti, Michele Aieta, Stefania De Faveri, Maria Chiara Scaini, Luciana Possidente, Leon W.M.M. Terstappen, Rita Zamarchi. Non small cell lung cancer and circulating tumor cell: A different expression of EpCam and cytokeratins. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 387. doi:10.1158/1538-7445.AM2015-387