Lee Gi-Hoon, Joo Young-Eun, Koh Yang-Seok, Chung Ik-Joo, Park Young-Kyu, Lee Jae-Hyuk, Kim Hyun-Soo, Choi Sung-Kyu, Rew Jong-Sun, Park Chang-Soo, Kim Sei-Jong
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Eur J Gastroenterol Hepatol. 2006 Sep;18(9):957-63. doi: 10.1097/01.meg.0000230086.83792.56.
BACKGROUND/AIMS: Survivin, a member of inhibitors of apoptosis, has been found in various human cancers. Its expression is associated with tumor progression and adverse outcome. Angiogenesis is an essential process for the primary tumor to grow and invade the adjacent normal structures. Angiogenic factors such as vascular endothelial growth factor induce survivin expression in endothelial cells. The current study was designed to investigate the possible role of survivin and vascular endothelial growth factor status for angiogenesis in human gastric cancer.
In this study, we conducted an immunohistochemical investigation of survivin and vascular endothelial growth factor expression in 106 tissue samples obtained from gastric cancer patients undergoing surgical treatment. To assess tumor angiogenesis, microvessel density was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody.
The positive expression of survivin and vascular endothelial growth factor in gastric cancer tissues was demonstrated in 50.0 and 69.8% of cases, respectively. The expression of survivin did not associate with vascular endothelial growth factor expression. Expression of survivin was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival (P=0.011, 0.004, 0.020, 0.002, 0.046, respectively). High microvessel density was significantly associated with lymph node metastasis and poor survival (P=0.006 and 0.017, respectively). The mean microvessel density value of survivin positive tumors was 87.4+/-34.4 and significantly higher than that of survivin negative tumors (P=0.016). The mean microvessel density value of vascular endothelial growth factor positive tumors was 98.7+/-37.0 and significantly higher than that of vascular endothelial growth factor negative tumors (P=0.001). A combined analysis of survivin and vascular endothelial growth factor status showed that the mean microvessel density value of both positive tumors was 103.7+/-33.1 and significantly higher than that of both negative tumors (P<0.001).
These results suggest that survivin may play an important role in carcinogenesis by stimulating tumor angiogenesis in human gastric cancer.
背景/目的:生存素是凋亡抑制因子家族的一员,已在多种人类癌症中被发现。其表达与肿瘤进展及不良预后相关。血管生成是原发性肿瘤生长并侵袭邻近正常组织的一个重要过程。血管内皮生长因子等血管生成因子可诱导内皮细胞中生存素的表达。本研究旨在探讨生存素及血管内皮生长因子状态在人类胃癌血管生成中的可能作用。
在本研究中,我们对106例接受手术治疗的胃癌患者的组织样本进行了生存素和血管内皮生长因子表达的免疫组织化学研究。为评估肿瘤血管生成,使用抗CD34单克隆抗体对内皮细胞进行免疫组织化学染色来计数微血管密度。
胃癌组织中生存素和血管内皮生长因子的阳性表达率分别为50.0%和69.8%。生存素的表达与血管内皮生长因子的表达无关。生存素的表达与肿瘤大小、浸润深度、淋巴结转移、肿瘤分期及不良生存显著相关(P值分别为0.011、0.004、0.020、0.002、0.046)。高微血管密度与淋巴结转移及不良生存显著相关(P值分别为0.006和0.017)。生存素阳性肿瘤的平均微血管密度值为87.4±34.4,显著高于生存素阴性肿瘤(P = 0.016)。血管内皮生长因子阳性肿瘤的平均微血管密度值为98.7±37.0,显著高于血管内皮生长因子阴性肿瘤(P = 0.001)。生存素和血管内皮生长因子状态的联合分析显示,双阳性肿瘤的平均微血管密度值为103.7±33.1,显著高于双阴性肿瘤(P<0.001)。
这些结果表明,生存素可能通过刺激人类胃癌中的肿瘤血管生成在致癌过程中发挥重要作用。