The relation between bone marrow angiogenesis and the proliferation index Ki-67 in multiple myeloma

Abstract

Aim: Angiogenesis correlates with disease progression in various haematological malignancies. This study investigated the association between microvascular density (MVD) and the Ki-67 proliferation index (Ki-67 PI), bone marrow infiltration, and C reactive protein (CRP) in patients with multiple myeloma. Methods: Bone marrow MVD was examined in 44 biopsies at diagnosis and 15 in plateau phase by immunostaining the endothelial cells with a monoclonal antibody to CD34. The Ki-67 PI was evaluated by a double immunostaining technique using the monoclonal antibodies MIB-1 and CD38. Results: MVD, Ki-67 PI, bone marrow infiltration, and CRP were significantly higher in pretreatment patients than in controls and decreased in patients achieving plateau phase. MVD significantly correlated with Ki-67 PI and infiltration, and Ki-67 correlated with infiltration. Conclusion: In multiple myeloma, apart from being a marker of proliferative activity, Ki-67 is also associated with bone marrow angiogenesis and tumour burden.

Hypoxia-inducible factor (HIF)-1α suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction

“…Targeting HIF-1a in multiple myeloma in vivo P Storti et al angiogenesis by HIF-1a suppression was accompanied by a reduction of VEGF immunostaining and of the proliferative index, Ki67, that could be related to angiogenesis in MM, 6 although it did not reach a statistical significance. Finally, in line with our data, it has been previously reported that HIF-1a inhibition by RNA interference inhibits in vivo angiogenesis in mice in other tumor models.…”

“…1 Particularly, an increase of BM angiogenesis and osteoclastogenesis occurs with MM cell growth and proliferation and plays a critical role in the pathophysiology and progression of MM. [2][3][4][5][6][7][8] The angiogenic switch in MM is mainly sustained by the overproduction of vascular endothelial growth factors (VEGFs) by MM cells and the BM microenvironment. 2,9,10 Other proangiogenic molecules, such as basic fibroblast growth factor, 11,12 interleukin-8 (IL-8), 13 angiopoietin-1 14 and osteopontin 15 are involved in the pro-angiogenic process.…”

Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease

“…The progression of the disease in MM patients is accompanied by an accelerated angiogenesis and production of proteolytic enzymes (6,27). Furthermore, the growth of myeloma cells is regulated by a cytokine network in which IL-6 represents a major growth player.…”

Anormalidades citogenéticas e sua relação com a proliferação e a apoptose celular em portadores de mieloma múltiplo

“…Diversos autores observaram maior expressão de Ki-67 em plasmócitos de pacientes com características clínicas e laboratoriais sugestivas de doença agressiva e que apresentaram pior evolução clínica (Lockhorst et al, 1988;Drach et al, 1992;Alexandrakis et al 2004a;Alexandrakis et al,2004b, Gastinne et al, 2007.…”

“…Diversos estudos, utilizando-se destas metodologias, evidenciaram que no MM com proporção elevada de células tumorais em divisão ocorre evolução clínica adversa Durie et al, 1980;Gerdes et al, 1983;Lokhorst et al, 1988;Drach et al, 1992;Schlüter et al, 1993;Thaler et al, 1994;Garcia-Sanz et al, 1995;San Miguel et al, 1995;GarciaSanz et al,1999;Alexandrakis et al, 2004a;Alexandrakis et al, 2004b;Greipp, Kumar, 2005;Gastinne et al, 2007) . Por outro lado, não existem muitos dados na literatura a respeito da importância da fração de plasmócitos em apoptose na evolução destes pacientes (Lichtenstein et al, 1995;Xu et al, 1997;Witzig et al, 1999;Xu et al, 2002;Scudla et al, 2006) .…”