Survivin、NF-κB、VEGFR-2在食管小细胞癌中的表达及其与甲磺酸阿帕替尼疗效的相关性

Expression of Survivin,NF-κB and VEGFR-2 and their relationship with Apatinib therapy in small-cell carcinoma of esophagus

目的探讨食管小细胞癌Survivin、NF-κB和血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR-2)的表达及其与甲磺酸阿帕替尼疗效的相关性。方法采用免疫组化SABC法检测36例食管小细胞癌Survivin、NF-κB、VEGFR-2的表达,并计数微血管密度(microvascular density,MVD)和微淋巴管密度(micro-lymphatic vessel density,MLVD),分析各指标与MVD、MLVD计数及甲磺酸阿帕替尼疗效的关系。结果 Survivin、NF-κB和VEGFR-2在食管小细胞癌中的阳性表达率分别为22.22%、66.67%和80.56%。Survivin、MLVD与食管小细胞癌淋巴结转移和浸润深度均无相关性(P>0.05)。VEGFR-2、NF-κB表达及MVD与淋巴结转移密切相关(P<0.05),与浸润深度无关(P>0.05)。NF-κB、VEGFR-2表达阳性者MVD明显高于阴性表达者(P<0.05)。NF-κB、VEGFR-2阳性组患者口服甲磺酸阿帕替尼治疗的疗效优于阴性组,而Survivin阳性、阴性组疗效差异无统计学意义(P>0.05)。结论食管小细胞癌中的VEGFR-2、NF-κB表达及MVD均与淋巴结转移密切相关,NF-κB、VEGFR-2阳性表达可作为口服甲磺酸阿帕替尼靶向治疗的生物学参考靶标。

Objective To investigate the expression of Survivin,NF-κB ,and VEGFR-2 as well as their relationships with treatment effects of Apatinib and with microvascular density and micro-lymphatic vessel density in small-cell carcinoma of esophagus. Methods Immunohistochemistry was used to assess expression of Survivin,NF-κB and VEGFR-2 as well as microvascular density and micro-lymphatic vessel density in 36 cases of small-ceU carcinoma of the esophagus. The results were compared with Apatinib treatment efficacy. Results Rates of positive expression were 22.22% for Survivin,66.67% for NF-κB and 80.56% for VEGFR-2. Lymphatic metastasis did not correlate with expression of Survivin, micro-lymphatic vessel density or tumor invasion depth. Lymphatic metastasis did correlate with expression of VEGFR-2, NF-κB and microvascular density,but not with tumor invasion depth. Microvascular density was higher in samples positive for NF-κB expression than in negative samples. Treatment effects of Apatinib were better in patients positive for NF-κB and VEGFR-2 expression than in expression-negative patients;treatment effects,however,did not vary with Survivin expression status. Conclusion Tumor lymphatic metastasis correlated significantly with VEGFR-2, NF-κB and microvascular density NF-κB and VEGFR-2 may play an important role in small-cell carcinoma and may be useful biomarkers in Apatinib therapy.