口腔鳞癌中Angiopoietin-2的表达与肿瘤血管生成及成熟的关系研究

The Studies on Relationship between the Expression of Angiopoietin-2 in Oral Squamous Cell Cacinoma and Its Significance for Angiogenesis and Vessel Maturation

  • 摘要: 目的: 近来研究表明Angiopoietin-2(Ang-2)在许多富血管肿瘤中有高水平的表达,被认为是一种重要的血管生成促进因子。然而它在口腔鳞癌中的表达情况及其意义尚不清楚。本文探讨Ang-2在口腔鳞癌中的表达及其与临床病理学特征和微血管密度(MVD)、血管成熟指数(VMI)间的关系;并评估Ang-2与血管内皮生长因子(VEGF)的联合表达在肿瘤血管生成及血管成熟中的作用。 方法: 用常规的免疫组织化学的方法检测41例口腔鳞癌及30例癌旁正常组织和10例正常口腔黏膜中的Ang-2及VEGF的表达;通过双标免疫组织化学法同时染CD34(标记所有血管内皮细胞)和平滑肌肌动蛋白(标记血管壁细胞包括血管平滑肌细胞和周细胞)评估MVD及VMI。 结果: Ang-2在口腔鳞癌组织中阳性表达者有21例(51.22%);Ang-2表达主要定位于肿瘤细胞胞浆;Ang-2在口腔鳞癌组织中表达显著高于癌旁正常组织(P<0.05)和正常口腔黏膜组织中Ang-2的表达(P<0.01);Ang-2表达与肿瘤的淋巴结转移密切相关(P<0.01),而与患者的性别、年龄和TNM分期及肿瘤分化程度无关(P均>0.05);Ang-2表达阳性的口腔鳞癌组织中MVD显著高于Ang-2表达阴性组(P<0.05)而VMI显著低于Ang-2表达阴性组(P<0.05)。在联合VEGF表达的情况下,同时表达Ang-2和VEGF的肿瘤MVD(51.08±2.99)显著高于其他任何表达状况(P均<0.05)。 结论: Ang-2在口腔鳞癌组织中的过表达可能在口腔鳞癌的进展过程中起重要作用,并与肿瘤的血管生成和成熟密切有关。

     

    Abstract: Objective : To investigate the correlations among the expression of Ang-2 to the clini-copathologic parameters, microvessel density (MVD) and vessel maturation index (VMI) in OSCC, and evaluated the significance of expression of Ang-2 in association with vascular endothelial cell growth factor (VEGF) in tumor angiogenesis and vessel maturation. Methods : The expression of Ang-2 and of VEGF were studied in 41 cases with OSCCs, 30 paraneoplastic oral tissues and ten normal oral mucosa by conventional immumohistochemistry. MVD and VMI were also assessed with double -labeling immumohistochemistry staining against CD34, a marker of pan -endothelial cells, and that against alpha-smooth muscle actin (-SMA), a marker of mural cells (pericytes/smooth muscle cells). Results : Of the 41 OSCC tissues, 21 (51.22%) Ang-2 were positive. Ang-2 was mainly detected in cytoplasm of OSCC.The expression of Ang-2 was significantly higher in OSCC than in adjacent noncancerous oral tssues (P<0.05) and normal oral mucosa (P<0.01). In the cunicoDathologic parameters, Ang -2 expression was closely correlated with lymph node metastasis of the tumor (P<0.01), but there was no significantly correlation among the Ang-2 expression and patients' sex, age and TNM stages and tumor's differentiated degree (all P>0.05). The MYD of positive-Ang-2 OSCC was significantly higher than that of negative-Ang-2 OSCC (P<0.05) while Y M I of positive-Ang-2 OSCC was significantly lower than that of negative-Ang-2 OSCC (P<0.05). When Ang-2 expression was combinated with the staus of YEGF exprssion, MYD of positive-Ang-2 and positive-VEGF expression were significantly high (51.08±2.99) as compared with that of other status in patient with OSCC (all P<0.05). Conclusion : These results suggest that overexpression of Ang -2 may play a crucial role in the development of OSCC. It is closely associated with angiogenesis and vessel maturation of the tumor.

     

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