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

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-1positive 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.

Author(s) Details

Dr. Larissa Bubnovskaya,
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Vasilkovskaya Str. 45, Kiev-03022, Ukraine.

Dr. Irina Ganusevich,
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Vasilkovskaya Str. 45, Kiev-03022, Ukraine.

Dr. Victor Mikhailenko
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Vasilkovskaya Str. 45, Kiev-03022, Ukraine.

Dr. Dmitry Osinsky,
City Clinical Oncological Center, Verchovynna Str.69, Kiev-03115, Ukraine.

Sergej Merentsev
City Clinical Oncological Center, Verchovynna Str.69, Kiev-03115, Ukraine.

Professor Sergej Osinsky,
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Vasilkovskaya Str. 45, Kiev-03022, Ukraine.

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