title: Significance of heparanase-1 and vascular endothelial growth factor in adrenocortical carcinoma angiogenesis: potential for therapy.
abstract: The purpose of this study was to determine the correlation between human adrenocortical carcinoma (ACC) and the proteins involved in tumor angiogenesis, and to evaluate the angiogenic status of ACC. The expression of heparanase-1 (HPA-1), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor-2 (VEGFR-2) as well as microvessel density (MVD) were measured in a series of tissue samples from 44 human sporadic adrenocortical tumors by immunohistochemistry. These specimens were classified as adenomas (n = 20) and carcinomas (n = 24) according to the histological criteria defined by Weiss. A total of 22 of 24 (91.67%) malignant cases showed positive staining for HPA-1 and 3 of 20 (15%) benign cases showed positive, the difference of HPA-1 expression between ACA and ACC was statistically significant (P < 0.001). Similarly, VEGF staining was seen in 70.83% (17/24) of the malignant cases versus 25% (5/20) of the benign, the difference of VEGF expression among two groups was statistically significant (P = 0.002). VEGFR-2 expressed highly in the ACC group (79.17%, 19/24) and lowly in the benign group (25%, 5/20), the two groups had extremely significant difference (P < 0.001). Malignant cases showed higher MVD compared to benign tumors (84.70 ± 12.44 vs. 21.05 ± 8.07, P < 0.001). HPA-1 and VEGF expression were positively correlated with MVD in all specimens (r_s = 0.812, P = 0.001; r_s = 0.834, P < 0.001). In conclusion, these results suggest that angiogenesis of human ACC maybe mediated by these proteins and they could represent selective targets for the molecularly targeted treatments of ACC.
authors.affiliation: Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, No. 197, Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Yun-Ze
authors.initials: YZ
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhou-Jun
authors.initials: ZJ
authors.lastname: Shen
authors.forename: Jia-Yan
authors.initials: JY
authors.lastname: Sheng
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: He
authors.forename: Gui
authors.initials: G
authors.lastname: Ma
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Qi
authors.forename: Ju-Ping
authors.initials: JP
authors.lastname: Zhao
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Wu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Rui
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000236:Adenoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D016037:Single-Blind Method; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099175:Heparanase