鼻咽癌组织内四种肿瘤相关蛋白表达及其与微血管密度和颈淋巴转移的关系

目的 研究人类前列腺癌转移抑制基因（kang ai 1，KAI1）、肿瘤转移抑制基因（nonmetastasis23，nm23）、E26转录因子（E26 transformation-specific-1，ETS-1）、血管内皮生长因子（vascular endothdial growth factor，VEGF）在鼻咽癌组织中的表达，并用CD34标记微血管测定密度，探讨它们之间的相关性及其与鼻咽癌淋巴转移和预后的关系。方法 应用免疫组织化学Envision二步法检测首诊时有颈淋巴转移的鼻咽非角化性癌（non-keratinizing carcinoma，NKC）50例、无淋巴转移的NKC30例和30例鼻咽黏膜慢性炎症组织内KAI1、nm23、ETS-1、VEGF蛋白的表达水平，并分析与NKC组织内微血管密度的关系。结果 KAI1、nm23蛋白在颈淋巴转移组、无颈淋巴转移组和鼻咽黏膜慢性炎症组织中的阳性表达率依次递增（χ^2=6．2，P〈0．05；χ^2=7．4，P〈0．01）；ETS-1、VEGF蛋白在3组间的阳性表达率依次递减（χ^2=12．8，P〈0．01；χ^2=9．1，P〈0．01）。80例NKC病例中KAI1、nm23蛋白阳性表达者的微血管密度（microvascular density，MVD）分别低于其阴性表达者（t=2．4，P〈0．05；t=2．0，P〈0．05）；ETS-1、VEGF蛋白阳性表达者MVD分别高于其阴性表达者（t=2．6，P〈0．05；t=3．6，P〈0．01）。KAI1和nm23蛋白共同阳性表达较两者各自单独阳性表达时MVD降低（t=2．5，P〈0．05，t=2．3，P〈0．05）；淋巴转移率降低（χ^2=5．2，P〈0．01；χ^2=4．3，P〈0．05）；ETS-1和VEGF蛋白共同表达较两者单独表达时MVD增高（t=2．1，P〈0．05；t=2．2，P〈0．05），淋巴转移率增加（χ^2=4．1，P〈0．01；χ^2=4．1，P〈0．01），提示KAI1与nm23蛋白及ETS-1与VEGF蛋白的表达有相互协同的作用。KAI1与nm23蛋白及ETS-1与VEGF蛋白阳性表达成正相关关系（r=0．5，P〈0．05；r=0．4，P〈0．01）。NKC患者有或无颈淋巴转移与治疗后5年生存期的高低差异有统计学意义（χ^2=4．4，P〈0．05）。结论 KAI1、nm23、ETS-1和VEGF蛋白的表达与鼻咽癌组织的微血管密度有明显相关性，与鼻咽癌的淋巴转移和预后密切相关，提示它们可以作为预测鼻咽癌颈淋巴转移及评估预后的参考指标。

Relationship between the expressions of KAI1,nm23,ETS-1,VEGF and microvascular density and clinical significance in nasopharyngeal carcinoma

OBJECTIVE: To investigate the relationship between the expressions of KAI1, nm23, ETS-1, vascular endothelial growth factor (VEGF) and microvascular density (MVD) and lymph node metastasis and prognosis in nasopharyngeal carcinoma (NPC). METHODS: The Envision immunohistochemical method was used to detect the expressions of KAI1, nm23, ETS-1 and VEGF in 50 cases of non-keratinizing carcinoma (NKC) with cervical lymph node metastasis, 30 cases of NKC without cervical lymph node metastasis at the primary diagnoses and 30 cases of non-tumor nasopharyngeal tissues (NP). The microvascular density was counted by immunostaining with CD34. RESULTS: (1) The expression rates of KAI1 and nm23 protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively , the difference being significant (P < 0.05); The expression rates of ETS-1 and VEGF protein in NKC with cervical lymph node metastasis group and without cervical lymph node metastasis group and NP group increased successively, the difference being significant (P < 0.05). (2) In 80 NKC cases, the MVD was respectively lower in KAI1 and nm23 protein positive groups than those in the negative groups (P < 0.05); the MVD was respectively higher in ETS-1 and VEGF protein positive groups than those in the negative groups (P < 0.05 ). (3) There was significant difference between the MVD, the number of NKC without cervical lymph node metastasis cases in the single expression of KAI1 or nm23 protein and in common expression of KAI1 and nm23 protein (P < 0.05), in the same as between the single expression of ETS-1 or VEGF protein and in common expressions of ETS-1 and VEGF protein (P < 0.05). (4) There was positive correlation between the expressions of KAI1 and nm23 protein (P < 0.01), as well as between the expressions of ETS-1 and VEGF protein (P < 0.01). (5) the 5-year survival rates of the patients correlated with cervical lymph node metastasis and the expressions of KAI1, nm23, ETS-1 and VEGF proteines in NKC (P < 0.05). CONCLUSIONS: The expressions of KAI1, nm23, ETS-1 and VEGF proteines were highly related to MVD in NPC,cervical lymph node metastasis and prognosis. They might be considered to be reference indicator for evaluating the cervical lymph node metastasis and prognosis of NPC.