Ippokratis Messaritakis 1 , Eleni Politaki 1 , Athanasios Kotsakis 1 , 2 , Eleftheria-Kleio Dermitzaki 2 , Filippos Koinis 2 , Eleni Lagoudaki 3 , Anastasios Koutsopoulos 3 , Galatea Kallergi 1 , John Souglakos 1 , 2 , Vassilis Georgoulias 1 , 2 , *
18 July 2017
To evaluate the phenotypic heterogeneity of circulating tumor cells (CTCs) based on the expression of proliferative, apoptotic and Epithelial-to-Mesenchymal Transmission (EMT) markers during front-line treatment in patients with small cell lung cancer (SCLC) and to evaluate their clinical relevance.
CTCs from 108 chemotherapy-naïve patients with SCLC were analyzed by double immunofluorescence staining using anti-Ki67, anti-M30, anti-Vimentin along with anti-CKs antibodies. In 83 patients CTCs were also enumerated using the CellSearch.
Sequential samples were available from 76 and 48 patients after one-treatment cycle and on disease progression (PD), respectively, for immunofluorescence and from 50 and 36 patients after one-cycle and on PD, respectively, for CellSearch. At baseline, 60.2% of the patients had detectable CTCs by either method. Both proliferative (CK67 +) and non-proliferative (Ki67 -), apoptotic (M30 +) and non-apoptotic (M30 -) as well as EMT (Vim +) CTCs were present in the same patient. Among 22 patients without detectable CTCs by CellSearch, CK +/Ki67 + and CK +/Vim + CTCs could be detected in 6 (27.3%) and 6 (27.3%) patients, respectively. One-chemotherapy cycle reduced both the incidence of detection ( p<0.001) and the absolute number ( p<0.001) of CTCs; conversely, on PD both the incidence of detection and the number of CTCs were significantly increased ( p = 0.002 and p = 0.04, respectively). Multivariate analysis revealed that the increased number of Vim + CTCs at baseline and of non-apoptotic CTCs on PD could be emerged as independent prognostic factors associated with decreased OS( p = 0.009 and p = 0.023, respectively).