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

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.
Methods: It was used immunocytochemistry (detection of DTCs, VEGFR-1 expression in BM);
immunohistochemistry (CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression); NMR spectroscopy
(level of tumor hypoxia), zymography (MMP-2 and MMP-9 activity, both in tumor and BM).
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 BM in patients with M0 (P<0.05). Overall survival (OS) of patients with category M0 and DTCs in BM
was shorter than that of patients without DTCs (P=0.0497). OS of patients with DTCs and Flt-1-
positive BM was shorter than that of patients without DTCs but with Flt-1-positive BM (P=0.0437).
Conclusion: Appearance of DTCs in BM correlates with hypoxia level in primary tumors. Detection of
DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.