Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression
Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression
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DOI：
10.1007/s00432-007-0310-1
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Takano, Yasuo
中科院分区：
文献类型：
--
作者：
Zheng, Hua-Chuan;Tsuneyama, Koichi;Takano, Yasuo
目的Pim-3是具有丝氨酸/苏氨酸激酶活性的原癌基因Pim家族成员，在肝、胰腺、结肠等内胚层来源器官的癌性病变中异常表达。方法采用免疫组化方法检测285例胃癌原发灶和37例胃癌组织芯片中Pim-3的表达，并与48例腺瘤和84例非癌粘膜组织芯片进行比较。结果Pim-3蛋白在腺瘤（64.6%）和胃癌转移灶（73.0%）中表达增强，在胃癌原发灶（39.3%）中表达较癌旁粘膜（13.1%）弱（P < 0.0001）。Pim-3在弥漫型胃癌中的表达水平高于浸润型胃癌（p = 0.018）。Pim-3表达与性别（p = 0.047）、淋巴结（p = 0.019）和静脉浸润（p = 0.014）密切相关。Pim-3表达与血管内皮生长因子（VEGF，p = 0.009）和细胞外基质金属蛋白酶诱导因子（EMMPRIN，p = 0.032）显著相关，这两种因子均被推测参与新血管形成，这是转移的关键步骤。相反，磷酸酶和张力蛋白同源性缺失的人10号染色体（Pten）阴性胃癌表现出较高的Pim-3表达比Pten阳性（p = 0.042）。胃癌组织中Pim-3表达与MVD无相关性（p = 0.715）。此外，Pim-3阳性胃癌患者，与Pim-3阴性胃癌患者相比，（p = 0.014）和Pim-3阳性也被确定为胃癌患者的独立预后因素结论Pim-3异常表达与胃腺癌的发生、发展有关，Pim-3异常表达与胃腺癌的发生、发展有关，Pim-3异常表达与胃腺癌的发生、发展有关。腺癌序列和随后的浸润和转移过程。此外，Pim-3还可用于预测胃癌患者的预后。不同的Pim-3表达是肠型和弥漫型癌分化的分子机制的基础。
Purpose Pim-3, a member of the proto-oncogene Pim family with serine/threonine kinase activity was aberrantly expressed in cancerous lesions of endoderm-derived organs such as liver, pancreas, and colon. The aim of this study was to clarify the role of Pim-3 expression in the tumorigenesis and the development of gastric carcinomas.Methods Pim-3 expression was immunohistochemically examined on the tissue microarrays containing primary (n = 285) and metastastic (n = 37) sites of gastric carcinomas, in comparison with adenoma (n = 48) and non-cancerous mucosa (n = 84). It was also compared with the clinicopathological parameters of gastric carcinomas.Results Pim-3 expression was enhanced in adenoma (64.6%) and metastasis sites of gastric carcinoma (73.0%), to a lesser degree in primary sites of gastric carcinoma (39.3%) when compared to non-cancerous mucosa (13.1%, p < 0.0001). Pim-3 expression levels were higher in intestinal-type than diffuse-type gastric carcinoma (p = 0.018). Pim-3 expression was closely correlated with sex (p = 0.047), lymphatic (p = 0.019) and venous invasion (p = 0.014). Pim-3 expression was correlated significantly with vascular endothelial growth factor (VEGF, p = 0.009) and extracellular matrix metalloproteinase inducer (EMMPRIN, p = 0.032), both of which are presumed to be involved in neovascularization, a crucial step for metastasis. On the contrary, phosphatase and tensin homology deleted from human chromosome 10 (Pten) negative gastric carcinomas exhibited higher Pim-3 expression than Pten positive ones (p = 0.042). There was no relationship between Pim-3 expression and MVD in gastric carcinomas (p = 0.715). Furthermore, patients with Pim-3 positive gastric cancer, showed a lower cumulative survival rate than those with Pim-3 negative gastric cancer (p = 0.014) and Pim-3 positive was also identified as an independent prognostic factor for gastric carcinoma patients (p = 0.006).Conclusions Aberrant Pim-3 expression was involved in gastric adenoma-adenocarcinoma sequence and subsequent invasion and metastasis process in gastric cancer. Moreover, Pim-3 may be employed to predict the prognosis of gastric cancer patients. Distinct Pim-3 expression underlies the molecular mechanisms for the differentiation of intestinal-type and diffuse-type carcinomas.