The relation between Endoglin (CD105), Thrombospondin-1 and VEGFR-3 and treatment results in metastatic colorectal cancer patients treated with bevacizumab combination therapy

Background: Angiogenesis is an important step in growth of malignant tumors. The relationship between efficacy and angiogenic factors such as CD105 (endoglin), thrombospondin-1 (TSP-1) and vascular endothelial growth factor receptor-3 (VEGFR-3) in patients with metastatic colorectal cancer (MCRC) treated with bevacizumab, antiangiogenic agent, combination chemotherapy were assessed.Patients and Methods: The clinicopathological data of 42 MCRC patients retrospectively analyzed. The expressions of CD105, TSP-1 and VEGFR-3 were examined in paraffin block of these patients by immunohistochemical staining. Patients had bevacizumab in combination with FOLFIRI, IFL, irinotecan only and FU/LV regimens.Results: Forty two patients with a median age of 55 years (range, 29-78) were evaluated. The median follow-up was 16 months (range, 3.3-41). The expression of TSP-1 and VEGFR-3 were 11.9% and 19%, respectively and 46% of patients showed widespread expression of CD105. The overall response rate, PFS and OS results according to treatment-line, CD105, TSP-1 and VEGFR-3 expressions as follows: in firs-line, 16.7%, 5 months and not reached and in salvage therapy, 26.7%, 6 and 15 months; in CD105 widespread staining group 13.3%, 6 and 10 months and in CD105 weak staining group 31.6%, 6 and 19 months; in TSP-1 positive group 0%, 6 and 13 months and in TSP-1 negative group 29.7%, 6 and 16 months; in VEGFR-3 positive group 12.5%, 6 and 15 months and in VEGFR-3 negative group 26.5%, 6 and 16 months, respectively.Conclusion: Non-significant treatment efficacy according to expression of these angiogenic markers in patients treated with bevacizumab combination chemotherapy showed that they have no clinically applicable prognostic significance in MCRC patients. Large prospective studies were necessary to establish this relationship clearly.