EpCAM-based Flow Cytometric Detection of Circulating Tumor Cells in Gallbladder Carcinoma Cases

Purpose: Liquid biopsy has entered the arena of cancer diagnostics in the past decade and detection of circulating tumor cells (CTC) is one diagnostic component. CTCs in gallbladder cancer (GBC) have hitherto not been comprehensively analysed. Methods and Results: The current study focused on the diagnostic role of CTCs in 27 cases of treatment-naive GBC and 6 normal controls as well as 6 cases of cholecystitis. An EasySep kit featuring negative immunomagnetic bead separation and flow cytometric detection of EpCAM positive and CD45 negative cells revealed CTCs in 25 of the 27 cases. At a cut-off point of ≥1, the CTC count discriminated GBC from controls with a sensitivity, specificity and diagnostic accuracy of 92.6%, 91.7% and 92.3%, respectively. CTC levels in turn correlated significantly with clinico-pathological parameters of cases in terms of known prognostic indicators, with significant diagnostic potential at a cut-off point of >4, to discriminate disease stage I and II vs. III and IV GBC. With a cut-off of >3, the CTC count discriminated tumor stages I and II vs. III and IV and at >6 CTCs could discriminate metastatic vs. non metastatic GBCs with a sensitivity, specificity and diagnostic accuracy of 55. 6%, 100.0% and 85.2, respectively. A review of CTC in pancreatico-biliary malignancies is included. Conclusion: Detection and quantification of CTCs may serve as a non-invasive biomarker for GBC diagnosis in correlation with radiological studies.