Vasculogenic mimicry and relevant regulatory factors in human retinoblastoma

ZHANG Li-na; ZHAO Gui-qiu; LIN Hong; WANG Qian; NIU Ying-jun

doi:10.3969/j.issn.1002-266X.2014.31.003

Abstract：Objective To observe the formation and origin of vasculogenic mimicry ( VM) in human retinoblastoma ( RB) and to investigate the roles of relevant regulatory factors .Methods We collected the human RB tissues to observe the formation of VM in human RB by HE staining and periodic acid-Schiff staining ( PAS)/CD34 double staining , and cal-culatee the VM density (VMD).The expression of ATP-binding cassette sub-family G member 2 (ABCG2), hemopoietic stem cell marker CD133(AC133), CD34, hypoxia inducible factor-1α(HIF-1α) and its downstream factors (EphA2 and matrix metalloproteinase 2 (MMP-2)) was detected by immunohistochemical method .The relationships among VM and the above indicators were analyzed by Pearson correlation analysis .Results HE staining showed blood vessels lined by endo-thelial cells as well as irregular lumen formed by tumor cells ( with red blood cells in it ) in some RB tissues .PAS/CD34 double staining showed 23 cases of positive VM (53.48%) in 43 RB samples, VMD was (26.52 ±8.72)/HP;the VM positive rate was negatively correlated with RB differentiation degrees (r =-0.532), and no significant correlation with the clinical stages .ABCG2 positive cells in the VM positive RB tissues were significantly more than those in the VM nega-tive RB tissues (P<0.01), a part of tumor cells expressed AC133 in the VM positive tissues, but not in the VM negative tissues, and only CD34 positive expression was observed in the vascular endothelial cells of all RB tissues .The expression of HIF-1α, EphA2 and MMP-2 in the VM positive group was significantly higher than that in the negative group ( all P<0.01), and the VMD is positively correlated with the three factors (all P<0.01; r=0.694, 0.630 and 0.795, respec-tively) .Conclusion VM exists in the poorly differentiated RB tissues , and its tube wall may mainly derive from ABCG 2 positive cancer stem cells .The up-regulated expression of HIF-1α, EphA2 and MMP-2 may promote the VM formation .