Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance

Abstract

Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia. Patients and Methods. 89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results. DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P < 0.024). DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0 was shown (P < 0.0248). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0 (P < 0.05). Overall survival (OS) of patients with M0 and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only) (P = 0.0497). Conclusion. Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.