血管生成和p16、p53蛋白表达与非小细胞肺癌淋巴结转移的相关性研究

Correlation of angiogenesis and aberrant expression of p16, p53 proteins with lymph node metastasis in nonsmall cell lung cancer

目的 分析非小细胞肺癌 (NSCLC)淋巴结转移与血管生成及p16、p5 3蛋白表达的关系。方法 采用免疫组织化学方法对 187例NSCLC(74例腺癌、76例鳞癌和 37例腺鳞混合癌 )进行血管染色计数和p16、p5 3蛋白测定 ,并作相关临床因素分析。结果 非小细胞肺癌组织中微血管密度平均为 6 .8± 3.3,p16和p5 3蛋白阳性表达率分别为 4 7.6 %和 34.2 %。各组织类型非小细胞肺癌中淋巴结转移病例 (T2 N1～ 2 M0 )的微血管密度显著高于未转移者 (T2 N0 M0 ) ;在肺鳞癌和腺鳞癌中 ,p16和p5 3蛋白同时表达异常 (p16 -p5 3+ )与微血管密度增高有关 ,但与淋巴结转移无关 ;而在肺腺癌中 ,p16和p5 3蛋白同时表达异常与淋巴结转移有关 ,但与微血管密度无关。微血管密度和p16、p5 3蛋白表达异常与年龄、性别、病理类型及分化程度均无明显相关。结论 各组织类型非小细胞肺癌的淋巴结转移均与活跃的血管生成密切相关 ,其中在肺鳞癌和腺鳞癌中 ,血管生成与p16和p5 3基因表达异常有关。而在肺腺癌中 ,血管生成和p16、p5 3蛋白异常表达是影响其淋巴结转移的两项独立的因素。

Objective To analyse the relationship between the lymph node metastasis, the angiogenesis and expression of p53 and p16 proteins in non small cell lung cancer (NSCLC). Methods The microvessel density (MVD) and the p53 and p16 protein expression were measured by immunohistochemically in 187 patients with NSCLC (74 adenocarcinomas, 76 squamous cell carcinomas, and 37 adeno squamous carcinomas). Results The average MVD in NSCLC tumor tissue was 6.8±3.3. The positive expression rates of p16 and p53 proteins were 47.6% and 34.2% respectively. The MVD of NSCLC cases with metastasis (T 2 N 1～2 M 0 ) in any histologic types was significantly higher than that of cases without metastasis (T 2 N 0 M 0 ). In squamous and adenosquamous cell carcinomas, the abnormal expression of both p16 and p53 proteins was closely related with increased angiogenesis but not with lymph node metastasis. While in adenocarcinomas, the abnormal expression of both p16 and p53 proteins was closely related with lymph node metastasis but not with angiogenesis. Neither angiogenesis nor abnormal p16 and p53 expression was found to be related with age, sex, pathohistological types and cytodifferentiation. CONCLUSION The active angiogenesis in NSCLC of all histologic types was closely related with lymph node metastasis, among which the increased angiogenesis in squamous and adenosquamous cell carcinomas was related with abnormal expression of both p16 and p53 proteins. While in adenocarcinomas, angiogenesis and the abnormal p16 and p53 expression were two independent factors for lymph node metastasis.