喉癌组织中缺氧诱导因子1α和表皮生长因子受体的表达与微血管密度的关系

摘要

目的 分析喉癌组织中缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)、表皮生长因子受体(epidermal growth factor receptor,EGFR)的表达与CD105标记计数微血管密度(micro vessel density,MVD)的关系及其在评价喉癌生物学行为和预后中的价值.方法 回顾性分析1990年1月至2002年1月91例喉癌患者临床病理资料及随访结果,免疫组化法检测肿瘤组织中HIF-1α、EGFR的表达,CD105标记肿瘤组织中微血管并计数MVD.结果 HIF-1α的表达与肿瘤大小、TNM分期、T分期、淋巴转移和病理分级有关(P值均<0.05);EGFR表达与TNM分期、淋巴转移、病理分级和复发有关(P值均<0.05);MVD与喉痛部位分型、TNM分期、T分期、淋巴转移、远处转移和病理分级有关(P值均<0.05).HIF-1α、EGFR表达水平与MVD有关(F值为7.644和5.197,P值为0.001和0.025).HIF-1α与EGFR表达的相关分析差异有统计学意义(r=0.238,P=0.007).患者3年和5年生存率为56.1%和44.2%,Log-rank法单因素生存分析表明喉癌部位分型、TNM分期、HIF-1α和EGFR的表达与患者预后有关(P值均<0.05);Cox比例风险模型分析显示TNM分期和EGFR的表达为影响喉癌患者预后的独立危险因素(P值分别为0.049和0.041,RR值分别为1.300和2.417).结论 在喉癌发生和进展过程中存在HIF-1α与EGFR的异常表达,且对调节肿瘤血管生成有一定的作用,并与肿瘤的生物学行为和预后有关.%Objective Analyze the relationship between the expression of hypoxia-inducible factor-1α( HIF-1α)and epidermal growth factor receptor(EGFR) and CD105 micro vessel density (MVD) and their value in evaluating biologic behavior and prognosis in laryngeal cancer. Methods Ninty-one cases of laryngeal cancer were analyzed about their clinical and pathology data. In tumor tissue the expression of HIF-1α and EGFR was detected by immunohistochemistry and MVD was marked by CD105. Results The expression of HIF-1α was correlated with size, TNM stage, T stage, lymph node metastasis and histological grade( all P < 0. 05). The expression of EGFR was correlated with TNM stage, lymph node metastasis, histological grade and relapse(all P <0. 05). MVD was correlated with type, TNM stage, T stage, lymph node metastasis, metastasis and histological grade ( all P < 0. 05 ). The expression of HIF-1α and EGFR was correlated with MVD ( F value was 7. 644 and 5. 197 respectively, P value was 0. 001and 0. 025 respectively). The correlation between the expression of HIF-1α and EGFR was significant statistically( r = 0.238,P= 0.007). The survival rate of patients of 3 years and 5 years were 56.1% and 44.2% respectively. Survival analysis by Log Rank showed that prognosis of laryngeal cancer patients was correlated with type, TNM stage and the expression of both HIF-1αand EGFR. While Cox multiple factors analysis demonstrated that TNM stage and expression of EGFR were independent prognostic factor of laryngeal cancer. (P value was 0. 049 and 0. 041 respectively,RR was 1. 300 and 2. 417 respectively). Conclusions HIF-1α and EGFR are key molecular event during development and progression of laryngeal cancer, which act in regulating tumor angiogenesis as well, and show intimate relationship with biological behavior and prognosis of laryngeal cancer.