肺腺癌中表皮生长因子受体基因突变与ki-67表达的相关性分析  

The correlation between epidermal growth factor receptor gene mutation and ki-67 expression in lung adenocarcinoma

作　　者：张丽珍 路喜安[2] 孙磊 赵先进 王小灵 ZHANG Lizhen;LU Xian;SUN Lei;ZHAO Xianjin;WANG Xiaolin(Department of Clinical Laboratory,Changzhi City People's Hospital of Shanxi Medical University,Changzhi,Shanxi 046000,China;Department of Pathology,the First Hospital of Shanxi Medical University,Taiyuan,Shanxi 035000,China)

机构地区：[1]山西医科大学附属长治市人民医院检验科,山西长治046000 [2]山西医科大学第一医院病理科,山西太原035000

出　　处：《国际检验医学杂志》2021年第S02期129-134,共6页International Journal of Laboratory Medicine

摘　　要：目的探讨肺腺癌组织中ki-67的表达及表皮生长因子受体(EGFR)的突变情况,分析二者的相关性。方法运用聚合酶链反应(PCR)扩增产物直接测序法检测482例肺腺癌患者肿瘤组织中EGFR 19、21外显子突变情况;运用免疫组织化学法检测上述肿瘤组织中ki-67的表达情况。结果在482例肺腺癌组织中共有204例(42.3%)发生EGFR基因突变,原位腺癌(AIS)、微浸润性腺癌(MIA)、浸润性腺癌(IAC)中突变率分别是21.8%、37.1%、55.8%,且在侵袭组中的突变率(IAC)(55.8%)要显著高于非侵袭组(AIS/MIA)(30.0%),差异有统计学意义(χ2=33.219,P=0.000),在与临床病理特征的相关性分析中,本文发现EGFR基因突变与胸膜侵袭显著相关,差异具有统计学意义(χ2=8.697,P=0.003),而与性别、年龄、肿瘤大小、吸烟、淋巴结转移无关;ki-67与肺腺癌的侵袭性呈正相关,且在侵袭性组(IAC)中的表达水平要显著高于非侵袭组(AIS/MIA),差异有统计学意义(χ2=91.404,P=0.000),在与临床病理特征的相关性分析中本文发现,ki-67在男性、肿瘤≥3 cm、吸烟、侵袭胸膜以及淋巴结转移的肺腺癌患者中的阳性表达率高,差异有统计学意义(P=0.000),而与年龄、肿瘤位置无关;EGFR突变型的患者其ki-67阳性率要显著高于EGFR野生型患者,差异有统计学意义(χ2=10.188,P=0.001)。结论EGFR基因突变及ki-67的表达与肺腺癌的侵袭性正相关,两者可用于评估肺腺癌的进展;相对于EGFR野生型患者,EGFR突变型的肺腺癌患者其ki-67的阳性表达率更高,ki-67或许可以作为预测EGFR-TKIs药物有效性的生物学指标,并有望成为改善EGFR-TKIs耐药的新靶点。Objective To analyze the relationship between EGFR mutations and ki-67 in lung adenocarinoma.Methods The EGFR gene exons 19 and 21 of tumor tissue were amplified by polymerase chain reaction(PCR),followed by direct sequencing in 482 paraffin-embedded lung adenocarinoma tissue.Immunohistochemistry were used to detect the expression of ki-67 in the above tumor tissues.Results EGFR mutations were detected in 204 cases of 482(42.3%)patients with lung adenocarcinoma.The mutation rates in AIS,MIA,and IAC were 21.8%,37.1%,and 55.8%,respectively.The mutation rate in the invasive group(IAC)(55.8%)was significantly higher than that in the non-invasive group(AIS/MIA)(30.0%)(χ2=33.219,P=0.000).In the correlation analysis with clinicopathological features,we found that EGFR mutation was significantly associated with pleural invasion(χ2=8.697,P=0.003),but not related to gender,age,tumor size,smoking,lymph node metastasis.Ki-67 was positively correlated with the aggressiveness of lung adenocarcinoma,and the expression level in IAC was significantly higher than that in AIS/MIA(χ2=91.404,P=0.000).Patients harbouring EGFR mutations had significantly higher ki-67 positive rate(χ2=10.188,P=0.001),which indicated that ki-67 was positive corrlation with EGFR mutations.Conclusion EGFR mutations and ki-67 may be positive correlation with the invasion of lung adenocarcinoma and both of them can be used to assess the progress of lung adenocarcinoma.Ki-67 could be the biological marker for effectiveness evaluation of EGFR TKIs and is expected to become the new target for improving EGFR TKIs resistance.

关 键 词：肺腺癌 表皮生长因子受体 基因突变 KI-67 侵袭性 表皮生长因子受体 

分 类 号：R73[医药卫生—肿瘤]