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

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

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％,χ2 =6.38,P＜0.05）和对照组（16.67％,χ2=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（χ2=1.18,P＞0.05χ2=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（χ2=0.05,P＞0.05;χ2=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,=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,=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.

Objective To investigate the expression of Notchl, Delta-like ligand 4 （ DLIA）, hairy and enhancer of split-1 （HES-1）, mierovessel density （MVD）, lymphatic vessel density （MLD） in gastric carcino- ma, so as to discuss their roles in the development of gastric carcinoma. Methods Gastric carcinoma, paracan- cer 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 ex- pressions of Notchl, DLL4, HES-1 were detected by immunohistochemistry. Immunohistoehemical double taining was used to detect MVD and MLD. The relationships between Notchl, DLL4, HES-1 expression and angiogene- sis, lymphangiogenesis and their significances were analyzed. Results The positive rate of Notchl in gastric car- cinoma 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% ）, paraeancerous （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 paracan- cerous 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 paracancerousgroup （4.05±2.48, t=9.30, P〈0.05） and control group （3.99 ±1.56, t=10.32, P〈0.05）. The ex- pression 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 Notchl, HES-1 and tissues MVD, MLD （P 〉 0. 05 ）. Conclusion Notchl plays important roles in the development of gastric carcinoma. There are many anglo- genesis and lymphangiogenesis in gastric carcinoma. The expression of DLL4 in gastric carcinoma has certain effect in the formation of microvessel.