Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival.
Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival.
复制标题
血管紧张素II型卵巢癌中的1型受体表达及其与肿瘤血管生成和患者存活的相关性。
DOI：
10.1038/sj.bjc.6602961
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发表时间：
2006-02-27
影响因子：
8.8
通讯作者：
Kikkawa, F
中科院分区：
文献类型：
--
作者：
Ino, K;Shibata, K;Kajiyama, H;Yamamoto, E;Nagasaka, T;Nawa, A;Nomura, S;Kikkawa, F
血管紧张素 II 是肾素-血管紧张素系统中的主要效应肽，通过 1 型血管紧张素 II 受体 (AT1R) 发挥生长促进和血管生成因子的作用。我们最近在体外卵巢癌细胞系中证明，血管紧张素 II 通过 AT1R 增强肿瘤细胞侵袭和血管内皮生长因子 (VEGF) 分泌。本研究的目的是确定卵巢癌中 AT1R 的表达是否与临床病理参数、血管生成因子和患者生存相关。对卵巢癌组织 (n=67) 中的 AT1R、VEGF、CD34 和增殖细胞核抗原 (PCNA) 进行免疫组织化学染色分析。通过计数 CD34 阳性内皮细胞来分析肿瘤内微血管密度 (MVD)。 85%的检查病例中有1型血管紧张素II受体表达，其中55%呈强阳性。 1型血管紧张素II受体表达与VEGF表达强度和MVD呈正相关，但与组织学亚型、分级、FIGO分期或PCNA标记指数无关。在 AT1R 染色呈阳性的患者中，与 AT1R 染色呈阴性的患者相比，总生存期和无进展生存期显着较差（分别为 P=0.041 和 0.017），尽管在多变量分析中，VEGF（而非 AT1R）是独立的预后因素。这些结果表明，AT1R 与肿瘤血管生成和卵巢癌患者不良预后相关，表明其作为卵巢癌治疗策略中新分子靶点的临床潜力。
Angiotensin II, a main effector peptide in the renin–angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT1R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT1R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n=67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT1R, the overall survival and progression-free survival were significantly poor (P=0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT1R, although VEGF, but not AT1R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT1R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.
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8.8
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