乙酰肝素酶与鼻咽癌侵袭、转移和血管生成的相关性

Correlation of heparanase expression with invasion,metastasis and angiogenesis of nasopharyngeal carcinoma

目的观察鼻咽癌组织中乙酰肝素酶(heparanase,HPA)的表达情况,探索其与肿瘤侵袭、转移和新生血管生成的相关性。方法运用逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)和免疫组织化学染色技术检测HPAmRNA和蛋白在50例鼻咽癌和20例鼻咽正常组织中的表达情况,并结合鼻咽癌临床病理特征,分析HPA mRNA的表达与鼻咽癌侵袭、转移和微血管密度(microvessel density,MVD)之间的关系。结果鼻咽癌组织中HPA mRNA和蛋白的阳性表达率分别为60.0%(30/50)和56.0%(28/50),鼻咽正常组织中无HPA mRNA和蛋白阳性表达者。HPA mRNA阳性表达与鼻咽癌临床分期、淋巴结和远处转移等临床病理特征有关(P<0.05)。HPA mRNA阳性表达者的MVD值(43.86±4.93)显著高于阴性者(27.41±2.67,P<0.01)。结论HPA参与鼻咽癌侵袭与转移,促进鼻咽癌的新生血管生成,有望成为鼻咽癌药物治疗的靶向因子之一。

OBJECTIVE To investigate the expression of heparanase and its correlation with the invasion,metastasis and angiogenesis in nasopharyngeal carcinoma（NPC）.METHODS Heparanase mRNA and protein was detected by reverse transcriptionPCR（RT-PCR）and immunohistochemical staining method in 50 human NPC specimens and 20 normal nasopharyngeal tissues.Microvessel density（MVD）was measured by immunohistochemical staining method with CD34 monoclonal antibody.The correlation of Heparanase mRNA expression with the clinicopathological characteristics and MVD in NPC were studied.RESULTS The positive rate of heparanase mRNA and protein in the cancerous tissues was 60.0%（30/50）and 56.0%（28/50）respectively,while that in normal nasopharyngeal tissues was 0%（0/20）.The positive rate of heparanase mRNA was 25.00%（2/8） in patients with stage I,46.15%（6/13）with stage II,68.42%（13/19）with stage III and 90.00%（9/10）with stage IV.The positive expression of heparanase mRNA in T1＋T2 and T3＋T4 with neck lymph node and distant metastasis was 63.64%（7/11）and 90.00%（18/20） respectively,while that in T1＋T2 and T3＋T4 without metastasis was 23.08%（3/13）and 33.33%（2/6） respectively.The positive expression of heparanase mRNA was correlated with the clinical stage,the neck lymph node and distant metastasis in NPC（P0.05）.MVD in heparanase mRNA positive group（43.86± 4.93）was significantly higher than that in heparanase mRNA negative group（27.41±2.67,P〈0.01）.CONCLUSION Heparanase may promote the invasion,metastasis and angiogenesis of NPC.Heparanase may be a possible target for anticancer drug development.