国际肿瘤学杂志

国际肿瘤学杂志 ›› 2014, Vol. 41 ›› Issue (10): 789-792.doi: １０．３７６０／ｃｍａ．ｊ．ｉｓｓｎ．１６７３４２２Ｘ．２０１４．１０．０２１

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胃癌中Notch1、DLL4、HES-1表达与微血管、 微淋巴管生成的关系及意义

张富花, 何黎黎, 张锦华, 庄剑波, 吴正奇, 韩俭, 张建刚   

  1. 730000兰州，甘肃省第二人民医院消化科（张富花、张锦华、庄剑波）；兰州大学病原生物学研究所（何黎黎、韩俭）, 病理研究所（张建刚）;甘肃省武威肿瘤医院消化科（吴正奇）
  • 出版日期:2014-10-29 发布日期:2014-10-11
  • 通讯作者: 张富花，Ｅｍａｉｌ：ｚｈａｎｇｆｕｈｕａｌｙ＠１２６．ｃｏｍ E-mail:ｚｈａｎｇｆｕｈｕａｌｙ＠１２６．ｃｏｍ
  • 基金资助:

    甘肃省科技支撑计划（１０１１ＦＫＣＡ１２０）

Relationships between Notch1, DLL4, HES1 expression and angiogenesis, lymphangiogenesis of gastric carcinoma and their significances

ZHANG  Fu-Hua, HE  Li-Li, ZHANG  Jin-Hua, ZHUANG  Jian-Bo, WU  Zheng-Qi, HAN  Jian, ZHANG  Jian-Gang   

  1. Department of Gastroenterology, Second People′s Hospital of Gansu Province, Lanzhou 730000, China
  • Online:2014-10-29 Published:2014-10-11
  • Contact: ＺｈａｎｇＦｕｈｕａ E-mail:ｚｈａｎｇｆｕｈｕａｌｙ＠１２６．ｃｏｍ

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摘要： 目的　研究 Ｎｏｔｃｈ１、Ｄｅｌｔａ样分子４（ＤＬＬ４）、发状分裂相关增强子ｌ（ＨＥＳ１）在胃癌组织的表 达检测微血管密度（ＭＶＤ）和微淋巴管密度（ＭＬＤ），探讨它们在胃癌发生发展中的作用。方法　收集术后 切除的胃癌组织、距癌组织边缘 ＞６０ｍｍ的癌旁组织，同期胃镜下正常胃黏膜作为对照。将标本组织制作 组织芯片，用免疫组织化学染色法检测 Ｎｏｔｃｈ１、ＤＬＬ４和 ＨＥＳ１表达，免疫组织化学双染法检测 ＭＶＤ和 ＭＬＤ，分析 Ｎｏｔｃｈ１、ＤＬＬ４和 ＨＥＳ１表达与微血管、微淋巴管生成的关系及意义。结果 　Ｎｏｔｃｈ１在胃癌组 的阳性率为４８．３０％，显著高于癌旁组（２５．００％，χ ２＝６．３８，Ｐ＜０．０５）和对照组（１６．６７％，χ ２＝１０．１８，Ｐ＜ ０．０５）；ＤＬＬ４在胃癌组的阳性表达率为５５．９４％，与癌旁组（４５．７０％）和对照组（５６．６７％）之间的差异均无 统计学意义（χ ２＝１．１８，Ｐ＞０．０５；χ ２＝０．００５，Ｐ＞０．０５）；ＨＥＳ１在胃癌组的阳性率为 ３６．６４％，与癌旁组 （３４．４０％）和对照组（３３．３％）之间差异无统计学意义（χ ２＝０．０５，Ｐ＞０．０５；χ ２＝０．１１，Ｐ＞０．０５）。胃癌组 ＭＶＤ为２８．８４±１４．１７，高于癌旁组（１７．０２±８．５４，ｔ＝４．０３，Ｐ＜０．０５）和对照组（１６．６９±７．２１，ｔ＝５．０１，Ｐ＜ ０．０５）；胃癌组 ＭＬＤ为８．５５±４．９８，显著高于癌旁组（４．０５±２．４８，ｔ＝９．３０，Ｐ＜０．０５）和对照组（３．９９± １．５６，ｔ＝１０．３２，Ｐ＜０．０５）。ＤＬＬ４表达与 ＭＶＤ有相关性（ｔ＝２．７７，Ｐ＜０．０５），与 ＭＬＤ无相关性（ｔ＝１．８９， Ｐ＞０．０５）。Ｎｏｔｃｈ１和 ＨＥＳ１表达与 ＭＶＤ和 ＭＬＤ之间无相关性（Ｐ＞０．０５）。结论　Ｎｏｔｃｈ１在胃癌发展中 具重要作用；胃癌中存在大量新生微血管、微淋巴管；胃癌中 ＤＬＬ４的表达在促进微血管的形成中有一定 作用。

关键词: 胃肿瘤, 受体, Ｎｏｔｃｈ１, 淋巴管, 微血管, Ｄｅｌｔａ样分子４；发状分裂相关增强子１

Abstract: ObjectiveTo investigate the expression of Notch1, Deltalike ligand 4 (DLL4), hairy and enhancer of split1 (HES1), microvessel density (MVD), lymphatic vessel density (MLD) in gastric carcinoma, so as to discuss their roles in the development of gastric carcinoma. MethodsGastric carcinoma, paracancer tissues which was apart from the edge of cancer tissue >60 mm obtained during operation and normal gastric mucosa obtained during gastroscopy were used as controls. All specimens were made tissue microarray. The expressions of Notch1, DLL4, HES1 were detected by immunohistochemistry. Immunohistochemical double taining was used to detect MVD and MLD. The relationships between Notch1, DLL4, HES1 expression and angiogenesis, lymphangiogenesis and their significances were analyzed. ResultsThe positive rate of Notch1 in gastric carcinoma was 48.30%, significantly higher than that of paracancerous (25.00%，χ2=6.38, P<0.05) and control group (16.67%，χ2=10.18, P<0.05). The differences of the positive rate of DLL4 in gastric carcinoma (55.94%), paracancerous (45.70%) and control group (56.67%) were not significant (χ2=1.18, P>0.05; χ2=0.005, P>0.05). The differences of the positive rate of HES1 in gastric carcinoma (36.64％), paracancerous (34.40%) and control group (33.33%) were not significant (χ2=0.05, P>0.05; χ2=0.11, P>0.05). The mean of MVD in gastric carcinoma group was 28.84±14.17, which was significantly higher than that in paracancerous group (17.02 ±8.54, t=4.03, P<0.05) and control group (16.69±7.21, t=5.01, P<0.05). The mean of MLD in gastric carcinoma group was 8.55±4.98, which was significantly higher than that in paracancerous group (4.05±2.48, t=9.30, P<0.05) and control group (3.99±1.56, t=10.32, P<0.05). The expression of DLL4 was correlated with MVD (t=2.77, P<0.05), but wasn′t correlated with MLD (t=1.89, P>0.05). There were no correlations between the expression of Notch1, HES1 and tissues MVD, MLD (P>0.05). ConclusionNotch1 plays important roles in the development of gastric carcinoma. There are many angiogenesis and lymphangiogenesis in gastric carcinoma. The expression of DLL4 in gastric carcinoma has certain effect in the formation of microvessel.

Key words: Ｓｔｏｍａｃｈｎｅｏｐｌａｓｍｓ, Ｒｅｃｅｐｔｏｒ, Ｎｏｔｃｈ１, Ｌｙｍｐｈａｔｉｃｖｅｓｓｅｌｓ, Ｍｉｃｒｏｖｅｓｓｅｌｓ, ＤＬＬ４, ＨＥＳ１