Circulating tumor cells in early stage lung adenocarcinoma: a case series report and literature review

// Xu-Rui Jin 1, * , Lu-Yao Zhu 1, * , Kai Qian 1 , Yong-Geng Feng 1 , Jing-Hai Zhou 1 , Ru-Wen Wang 1 , Li Bai 2 , Bo Deng 1 , Naixin Liang 3 , Qun-You Tan 1 1 Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China 2 Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China 3 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China * These authors contributed equally to this work Correspondence to: Bo Deng, email: deng.bo@dphospital.tmmu.edu.cn Naixin Liang, email: pumchnelson@163.com Qun-You Tan, email: tanqy001@163.com Keywords: lung adenocarcinoma, circulating tumor cells, AIS, EMT Received: September 14, 2016 Accepted: February 08, 2017 Published: February 19, 2017 ABSTRACT Purpose: The study aimed to monitor circulating tumor cells (CTCs) in early stage lung adenocarcinoma patients. Results: CTCs were characterized and classified to epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs, as per epithelial-mesenchymal transition(EMT) biomarkers. CTCs could not be found in healthy controls. However, in cohort A, CTCs were found in 17 (17/18) cases. Detection rate of E-CTCs was lower (5/18) compared with M-CTC (10/18) or E&M-CTC (14/18). Highly abundant M-CTCs were prone to being in the tumors > 2 cm. In cohorts A and B, CTCs count increased significantly in all patients with tumor progression (7/7). Higher CTCs level or change range could be found postoperatively in the patients with tumor progression, as compared with patients with disease free survival ( P < 0.01). Additionally, CTCs detected by CanPatrol TM could be validated by CytoploRare or Pep@MNPs. Materials and Methods: We included four cohorts of patients and 20 healthy controls. In cohort A, CTCs were detected by a newly established approach, i.e., CanPatrol TM , prior to anesthesia and monitored after operation longitudinally. In cohort B, CTCs were not assessed prior to operation, but were longitudinally detected after operation. For validation, we detected FOLR(+)-CTCs by using CytoploRare and EPCAM(+)-CTCs by using Pep@MNPs prior to operation, in cohorts C and D, respectively. Conclusion: CTCs can be detected in early stage lung adenocarcinoma, even in adenocarcinoma in situ , and CTCs detection can effectively monitor tumor progression. The distinguishing of biomarkers of highly invasive and aggressive CTCs warrants further robust study.