Cytokeratin-based ctc counting unrelated to clinical follow up

Ludmilla Thomé Domingos Chinen, Fernanda Machado de Carvalho, Bruna Maria Malagoli Rocha, Caroline Motta Aguiar, Emne Ali Abdallah, Daniel Campanha, Natália Breve Mingues, Thiago Bueno de Oliveira, Macello Sampaio Maciel, Gustavo Marchioro Cervantes, Aldo L.A. Dettino, Fernando Augusto Soares, Patrizia Paterlini-Bréchot, Marcello Ferretti Fanelli


Background: Circulating tumor cells (CTCs) have been reported to be a relevant prognostic biomarker in metastatic patients. However, their clinical use and impact is still under debate. We have thus comparatively and kinetically assessed two CTC detection methods according to the patient’s clinical follow up.
Methods: CTC counting and characterization were repeatedly performed during follow up in a patient with metastatic undifferentiated non-small cell lung cancer by using cytokeratin (CK)-dependent immunomagnetic separation (Miltenyi) and CK-independent, size-based isolation [isolation by size of tumor cells (ISET)] (Rarecells).
Results: Comparison between the two methods showed a parallel increase of CTC detected by ISET and worsening of the clinical status, while CK-dependent CTC numbers were decreasing, misleadingly suggesting a response to treatment. ISET results were in agreement with the clinical follow up showing Circulating tumor microemboli (CTM) and CTC expressing a mesenchymal marker with absence of epithelial markers.
Conclusions: This case report study shows the interest of a comparative and kinetic analysis of different methods for CTCs detection combined with their evaluation according to the clinical follow up. Our results should open up an area for future research and validation in larger clinical cohorts.