口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2的表达及临床意义

背景与目的:近来研究表明Angiopoietin-1、Angiopoietin-2(Ang-1、Ang-2)是极有潜力的血管生长因子,它们与其它血管生长因子之间的局部平衡关系决定了血管是进展、稳定还是衰退。本文探讨Ang-1及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(microvesseldensity,MVD)、血管成熟指数(vesselmaturationindex,VMI)之间的关系,并评估Ang-1及Ang-2的联合表达在肿瘤血管生成及成熟中的作用。方法:用常规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例正常口腔粘膜中的Ang-1及Ang-2的表达;通过双标免疫组织化学法同时检测CD34和α-平滑肌肌动蛋白,评估MVD及VMI。结果:口腔鳞癌组织与癌旁正常组织及正常口腔粘膜相比,Ang-2的表达显著增加(51.22%vs.26.67%,0%),而Ang-1的表达显著降低(41.46%vs.90.00%,90.00%),P值均<0.05;在癌旁正常组织与正常口腔粘膜之间,二者的表达没有显著性差异(P均>0.05)。对临床病理因素的分析发现,在高分化肿瘤中Ang-1的阳性率显著高于中分化肿瘤(56.00%vs.18.75%,P<0.05);而Ang-2的阳性率在有淋巴结转移的肿瘤显著高于无淋巴结转移肿瘤(84.62%vs.35.71%,P<0.01)。Ang-1和Ang-2的表达与肿瘤的血管生成及血管成熟密切相关(P值均<0.05)。联合Ang-1和Ang-2的表达发现,Ang-1与Ang-2相互拮抗共同调节肿瘤的血管成熟。结论:口腔鳞癌中Ang-1表达降低及Ang-2表达增高与肿瘤血管的生成及成熟密切相关。

Expression and significance of angiopoietin-1 and angiopoietin-2 in oral squamous cell cacinoma

BACKGROUND & OBJECTIVE: Recently, Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) have been identified as potential angiogenic factors. The local balance between them and other angiogenic factors determines the growth, stableness, or regression of blood vessels. This study was to investigate the correlations of Ang-1 and Ang-2 expression to clinicopathologic features, microvessel density (MVD), and vessel maturation index (VMI) of oral squamous cell cacinoma (OSCC), and evaluate the significance of Ang-1 and Ang-2 coexpression in tumor angiogenesis and vessel maturation. METHODS: The expression of Ang-1 and Ang-2 in 41 specimens of OSCC, 30 specimens of adjacent noncancerous oral tissues, and 10 specimens of normal oral mucosa was detected by immunohistochemistry. MVD and VMI were assessed with double-labeling immunohistochemical staining against CD34 and alpha-smooth muscle actin (alpha-SMA). RESULTS: The positive rate of Ang-1 was significantly lower in OSCC than in adjacent noncancerous oral tssues and normal oral mucosa (41.46% vs. 90.00% and 90.0%, P < 0.05); the positive rate of Ang-2 was significantly higher in OSCC than in adjacent noncancerous oral tssues and normal oral mucosa (51.22% vs. 26.67% and 0, P < 0.05). The differences in Ang-1 and Ang-2 expression between adjacent noncancerous oral tssues and normal oral mucosa were not significant (P > 0.05). The positive rate of Ang-1 was significantly higher in highly differentiated tumor than in moderately differentiated tumor (56.00% vs. 18.75%, P < 0.05); the positive rate of Ang-2 was significantly higher in tumor with lymph node metastasis than in tumor without lymph node metastasis (84.62% vs. 35.71%, P < 0.01). Ang-1 and Ang-2 expression were closely correlated with angiogenesis and vessel maturation of tumor (P < 0.05). Ang-1 and Ang-2 had antagonistic effect on the regulation of tumor vessel maturation. CONCLUSION: The down-regulation of Ang-1 and up-regulation of Ang-2 are closely related to tumor angiogenesis and vessel maturation.