非小细胞肺癌组织中Ki-67和血管内皮生长因子受体2及微血管密度的表达及其与阿帕替尼疗效的关系

Expressions of Ki-67 and vascular endothelial growth factor receptor 2 and microvascular density in non-small cell lung cancer tissue and their associations with efficacy of apatinib

目的探讨非小细胞肺癌(NSCLC)患者肿瘤组织中Ki-67、血管内皮生长因子受体2(VEGFR-2)和微血管密度(MVD)的表达及其与阿帕替尼疗效的关系。方法选取哈尔滨医科大学附属肿瘤医院2020年1月至2022年8月期间收治的晚期NSCLC患者42例,采用免疫组化法检测患者肿瘤组织中Ki-67、VEGFR-2和CD34表达,测定MVD,探讨Ki-67、VEGFR-2表达和MVD水平与患者临床特征的关系,分析不同VEGFR-2、Ki-67、MVD表达水平NSCLC的阿帕替尼临床疗效。结果Ki-67、VEGFR-2、MVD高表达率分别为52.4%(22/42)、69.0%(29/42)、54.8%(23/42),MVD均值为22.42个/视野。单因素分析结果显示,肿瘤分化程度和淋巴结转移与Ki-67高表达、MVD高水平相关(均P<0.05)。肿瘤淋巴结转移与VEGFR-2高表达相关(P<0.05)。VEGFR-2、Ki-67、MVD均与性别、年龄、美国东部肿瘤协作组(ECOG)评分、是否吸烟、肿瘤病理类型、有无肺外转移无关(均P>0.05)。多因素分析结果显示,肿瘤低分化(OR=11.265,95%CI:2.948~39.925,P=0.009)是Ki-67高表达的独立影响因素,淋巴结转移(OR=8.689,95%CI:1.215~62.122,P=0.031)是VEGFR-2高表达的独立影响因素(均P<0.05)。在阿帕替尼治疗后,MVD高表达与NSCLC患者高ORR相关,Ki-67、VEGFR-2、MVD高表达与NSCLC患者高DCR有关。结论肿瘤分化程度是Ki-67高表达的独立影响因素,淋巴结转移是VEGFR-2高表达的独立影响因素。Ki-67、VEGFR-2和MVD三者联合检测在二线及以上阿帕替尼治疗方案中具有一定的疗效预测价值。

Objective To investigate the expressions of Ki-67,vascular endothelial growth factor receptor 2(VEGFR-2)and microvascular density(MVD)in non-small cell lung cancer(NSCLC),and their associations with the efficacy of apatinib.Methods Forty-two patients with advanced NSCLC admitted to the Affiliated Tumor Hospital of Harbin Medical University from January 2020 to August 2022 were selected.The expressions of Ki-67,VEGFR-2 and CD34 in tissues of patients were detected by immunohistochemical method,and MVD was measured.The association between expressions of Ki-67,VEGFR-2 with levels of MVD and clinical characteristics of patients were determined.The clinical efficacy of apatinib between different expressions of Ki-67,VEGFR-2 and MVD were also determined.Results The high expression rates of Ki-67,VEGFR-2,and MVD were 52.4%(22/42),69.0%(29/42),and 54.8%(23/42),respectively,with a mean MVD of 22.42 per field.Univariate analysis showed that the degree of tumor differentiation and lymph node metastasis were correlated with high expressions of Ki-67 and high levels of MVD(all P<0.05).Tumor lymph node metastasis was associated with high expression of VEGFR-2(P<0.05).Expressions of VEGFR-2,Ki-67 and MVD were not correlated with gender,age,Eastern Cooperative Oncology Group(ECOG)rating,smoking history,pathological type of tumor or extrapulmonary metastasis(all P>0.05).Multivariate analysis showed that low tumor differentiation(OR=11.265,95%CI:2.948-39.925,P=0.009)was an independent influencing factor for Ki-67 high expression,while lymph node metastasis(OR=8.689,95%CI:1.215-62.122,P=0.031)was an independent influencing factor for VEGFR-2 high expression(all P<0.05).After the treatment regimen of apatinib,high expression of MVD was associated with high ORR in NSCLC patients,and high expressions of Ki-67,VEGFR-2 and MVD were associated with high DCR in NSCLC patients.Conclusions The degree of tumor differentiation is an independent influencing factor for Ki-67 high expression,and lymph node metastasis is an independent influencing factor for VEGFR-2 high expression.The combined detection of Ki-67,VEGFR-2 and MVD 3 has certain clinical efficacy prediction value in secondline and above apatinib treatment schemes.