Does the presence of disseminated tumour cells in bone marrow or circulating tumour cells predict early tumour recurrence in patients with oesophagogastric cancer?

Abstract

Oesophagogastric cancer is associated with poor long term survival; overall five-year survival is 10-15%. A significant proportion of patients who undergo curative surgery subsequently develop metastatic disease. Evidently, local control of the tumour does not eliminate the risk of haematogenic recurrence. The cancer cell biology of disseminated disease and the mechanisms of its development remain poorly understood. The presence of disseminated tumour cells in blood and bone marrow of patients with breast, colorectal and lung carcinoma are associated with poor prognosis. The aims of the study were to develop a reliable assay to identify circulating tumour cells (CTCs) in the blood and disseminated tumour cells (DTCs) in the bone marrow and characterize the prevalence, biology and heterogeneity of the cells in patients with oesophagogastric cancer by high resolution imaging flow cytometry and fluorescence activated cell sorting. The objective of the thesis was to evaluate the prognostic significance CTCs and DTCs in oesophagogastric cancer. Blood samples were taken from patients undergoing curative and palliative treatment for oesophagogastric cancer. Bone marrow from the rib section excised as part of an open oesophagetomy was collected. CTCs and DTCs were isolated from the blood and the bone marrow by red cell lysis and immunomagnetic removal of white blood cells. Enriched cells were incubated with antibodies against epithelial, mesenchymal and predictive biomarkers. CTCs and DTCs were identified based upon their morphology and biomarker expression by high resolution imaging flow cytometry. CTCs and DTCs were present in all patients undergoing curative and palliative treatment for oesophagogastric cancer. Post curative surgery, patients with 100 or more CTCs in the blood had a significant reduction in relapse free survival (p=0.012). The study highlights the prognostic potential of CTCs in the blood and DTCs in the bone marrow of patients undergoing curative and palliative treatment for oesophagogastric cancer.