3 and median value 12.9, range 1.4–75, respectively). Figure 1 Immunohistochemical staining of HIF-1α, LY2603618 mouse VEGF-A and VEGF-C in normal renal tissue (A-C) and clear cell renal cell carcinoma (CCRCC) (D-F). A homogeneous cytoplasmic staining of tubular cells and weak staining in glomerules was observed with HIF-1α (A), while VEGF-A and VEGF-C were positive in tubular cells, glomerular mesangium and interstitial macrophages (B and C). In CCRCC, HIF-1α immmunoreactivity buy AZD0156 was nuclear and/or cytoplasmic (D), while it was perimembranous and/or diffuse cytoplasmic for VEGF-A and VEFG-C (E and F). (magnification ×200). VEGF-A and C Immunohistochemical staining of VEGF-A was cytoplasmic, both in normal renal tissue and tumor cells, as
we described previously [15]. Immunohistochemical staining of VEGF-C was also cytoplasmic in normal renal tissue and CCRCC showing heterogeneous staining of different intensity and percentage of positive Apoptosis Compound Library tumor cytoplasm as well as perimembranous and/or diffuse staining pattern (Fig. 1). Division according to percentage of perimembranous or diffuse staining pattern turned out to be more important than intensity and/or percentage of positive
tumor cytoplasm in relation to HIF-1α or clinicopathologic parameters. The median value of perimembranous staining pattern was 12.7% (range 0–94%) for VEGF-A (pVEGF-A) and 46% (range 0–100%) for VEGF-C (pVEGF-C). The median value of diffuse cytoplasmic pattern was 10% (range 0–92%) for VEGF-A (dVEGF-A) and 26.3% (range 0–100%) for VEGF-C (dVEGF-C). Association between HIF-1α, VEGF-A and -C Nuclear HIF-1α demonstrated inverse correlation with dVEGF-A (p = 0.002) and almost so with dVEGF-C (p = 0.053), and showed no association with perimembranous
staining pattern of either VEGF-A or -C. Cytoplasmic HIF-1α correlated with both dVEGF-A (p < 0.001) and dVEGF-C (p = <0.001), and also showed inverse correlation with perimembranous staining pattern of VEGF-C (p < 0.001), but not VEGF-A (Table 1). Table 1 Relation of HIF-1α to VEGF-A and VEGF-C VEGF-A (%) VEGF-C (%) pVEGF-A dVEGF-A pVEGF-C dVEGF-C p1 rp 1 p1 rp 1 p1 rp 1 p1 rp 1 HIF-1α (%) nHIF-1α 0.535 0.068 0.002 -0.322 0.121 0.168 0.053 -0.209 cHIF-1α 0.094 -0.180 <0.001 0.526 <0.001 -0.629 <0.001 0.637 1Pearson's correlation Regarding association of VEGF-A and -C, Pearson's correlation showed a relation of only diffuse staining pattern of both proteins Sucrase (p < 0.001, rp = 0.586) with no association between the perimembranous staining patterns of the mentioned growth factors. Association of HIF-1α, VEGF-A and -C with clinicopathologic parameters There were 59 men and 35 women in the study. The median value of tumor size was 6.3 (1.8–17.5) cm. The Fuhrman nuclear grading distribution was as follows: 12 (12.8%) grade 1, 40 (42.6%) grade 2, 22 (23.4%) grade 3 and 20 (21.2%) grade 4 tumors. There were 71 (75.5%) tumors limited to the kidney (pT1 and pT2) and 23 (24.5%) tumors with extrarenal expansion (pT3 and pT4).