• Evangelos Terpos, Konstantinos Anargyrou, Eirini Katodritou, Efstathios Kastritis, Athanasios Papatheodorou, Dimitrios Christoulas, Anastasia Pouli, Eurydiki Michalis, Sosana Delimpasi, Maria Gkotzamanidou, Nikitas Nikitas, Vasilios Koumoustiotis, Dimitrios Margaritis, Konstantinos Tsionos, Ekaterini Stefanoudaki, John Meletis, Konstantinos Zervas, Meletios A Dimopoulos, and Greek Myeloma Study Group, Greece.
• Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. eterpos@med.uoa.gr
• Int. J. Cancer. 2012 Feb 1;130(3):735-42.

AbstractThe circulating levels of several angiogenic cytokines [angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang-1/Ang-2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin-1/angiopoietin-2 ratio correlated with advanced disease features including international staging system (ISS)-3 stage, renal impairment and extensive bone disease. Based on immunohistochemical results in 20 patients (10 with the higher and 10 with the lower values of circulating angiopoietin-2) we found that angiopoietin-2 is expressed by myeloma cells and correlates with increased microvessel density in subsets of patients. Furthermore, Ang-1/Ang-2 ratio correlated with survival. Patients with circulating Ang-1/Ang-2 below or equal to the median value (6.03) had a median survival of 26.3 months compared to 53 months of all others (p = 0.002). Interestingly, this was mainly observed in patients who received first-line therapy with novel agent-based regimens (65% of our patients). Furthermore, a subset of ISS-3 patients with serum Ang-1/Ang-2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang-1/Ang-2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50-2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents.Copyright © 2011 UICC.

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