Figure 2.
Histological finding of initial tumors revealing that tumor cells predominantly accumulated around the vessels (so-called vascular co-option). Hematoxylin and eosin staining (A) and CD34 (B), CA9 (C), HIF-1α (D), nestin (E), and FOXM1 expression (F). Photomicrograph of immunohistochemistry (×200) (bar = 100 μm). Note that CA9 expression was found in the perinecrotic tumor cells, and the expression of HIF-1α, nestin, and FOXM1 was widely distributed. Typical histological findings of “pseudo-papillary” structures resembling “vascular co-option” in recurrent tumors. Hematoxylin and eosin staining (G) and CD34 (H), CA9 (I), HIF-1α (J), nestin (K), and FOXM1 expression (L). Photomicrograph of immunohistochemistry (×200; bar = 100 μm); (×400; bar = 100 μm). Note that colocalization of FOXM1- and HIF-1α-positive cells was prominent in the perivascular area. Comparison of expression of FOXM1, MVD, and tumor oxygenation between the presence and absence of “pseudo-papillary” structures. FOXM1 (M), nestin (N), MVD (O), CA9 (P), and HIF-1α expression (Q). Error bar; standard deviation. CA9, carbonic anhydrase 9; FOXM1, Forkhead box M1; HIF-1α, hypoxia inducible factor-1 alpha; MVD, microvessel density.