EGFR、VEGF及Ki-67在肺浸润性腺癌和微浸润性腺癌及浸润前病变组织中的表达及意义

目的：探讨EGFR、VEGF及Ki-67在肺浸润性腺癌、微浸润性腺癌及浸润前病变组织中的表达，及其与临床病理特征之间的相关性。方法按照2011年IASLC/ATS/ERS多学科肺腺癌新分类方案，对2004年1月至2010年12月间日照市人民医院常规病理诊断中确诊为肺腺癌、细支气管肺泡癌和不典型腺瘤样增生的病例，使用和整合病理组织学、免疫组化TTF-1和P63或（和）CK5/6]及临床、影像学多学科知识，重新诊断、分类，应用免疫组织化学S-P法检测128例浸润性肺腺癌、28例微浸润性腺癌、46例浸润前病变（29例原位腺癌AIS、17例不典型腺瘤样增生）病理组织中EGFR、VEGF及Ki-67蛋白的表达，以30例癌旁组织、30例正常肺脏组织作对照，并结合临床病理特征进行相关性分析，比较EGFR、VEGF及 Ki-67：（1）在浸润性腺癌、微浸润性腺癌及浸润前病变三种不同组织中表达差异，及其与正常黏膜组织差异；（2）三者在28例微浸润性腺癌中微浸润灶与原位腺癌两种成分中表达的差异；（3）三者的表达与肿瘤大小、分化程度、浸润程度、淋巴结转移等临床病理因素的关系；（4）EGFR、VEGF及Ki-67三者在浸润性腺癌中表达的相关性。结果（1）EGFR、VEGF及Ki-67的表达在浸润前病变、微浸润性腺癌及浸润性肺腺癌组织中的表达依次增高，与正常对照组比较，差异有统计学意义（P＜0.01）。（2）EGFR、VEGF及Ki-67在微浸润性腺癌微浸润与原位两种成分中表达的差异无统计学意义（P＞0.05）；与浸润性腺癌比较，Ki-67表达差异有统计学意义（P＜0.05），EGFR、VEGF的表达差异无统计学意义（P＞0.05）。（3）肿瘤大小≤2 cm组与＞2 cm且＜3 cm组间比较，EGFR、VEGF及Ki-67表达差异有统计学意义（P＜0.05）；肿瘤大小＞2 cm且＜3 cm组与≥3 cm组比较，VEGF表达差异有统计学意义（P＜0.05），EGFR及Ki-67表达无明显差异（P＞0.05）。（4）EGFR、VEGF及Ki-67表达与组织学类型（鳞屑样、腺泡样、乳头状、实性）无关（P＞0.05）；EGFR 高表达与组织学分级低分化、淋巴结转移及肿瘤高分期有关（P＜0.05）；VEGF与组织学分级、淋巴结转移及肿瘤高分期均无关（P＞0.05）；Ki-67只与淋巴结转移有关（P＜0.05），而与组织学分级、肿瘤高分期无关（P＞0.05）。EGFR、VEGF 及 Ki-67三者表达正相关（P＜0.05）。结论本组显示原位腺癌大小以2 cm为界更能较好地显示生物学行为；EGFR、VEGF及Ki-67高表达与肺腺癌发生、浸润、转移密切相关，早期联合检测能辅助预测肺腺癌的生物学行为、评估预后和指导治疗。

Expression and clinical significances of EGFR,VEGF and Ki-67 in lung adenocarcinoma,minimally invasive adenocarcinoma and precancerous lesions

Objective To study the expression and clinical significance of epidermal growth factor receptor（EGFR）, vascular endothelial growth factor（VEGF）, and Ki-67 in lung invasive adenocarcinoma, minimally invasive adenocarcinoma（MIA） and precancerous lesionsadenocarcinoma in situ（AIS） and atypical adenomatous hyperplasia（AAH）]. Methods The expression of EGFR, VEGF and Ki-67 were investigated by immunhistochemical S-P method in 128 cases of lung invasive adenocarcinoma tissues, 28 cases of MIA, 46 cases of precancerous lesions（29 cases of AIS, 17 cases of AAH） and adjacent normal tissues and the correlation with pathological factors were analyzed. Results The expressions of EGFR, VEGF and Ki-67 increased from the tumor free tissues, precancerous lesions, MIA and lung invasive adenocarcinoma and there was a significant difference between lung invasive adenocarcinoma and precancerous lesions（AIS and AAH） and the tumor free tissue （P〈0.05）.However, there was no significant difference between lung invasive adenocarcinoma and minimally invasive adenocarcinoma, and there was no significant difference between minimally invasive adenocarcinoma and adenocarcinoma in situ, too. The expressions of EGFR, VEGF and Ki-67 were not related with the type of tumor （P〉0.05）. The expressions of EGFR were statistically correlated with the tumor size, grade, the degree of the infiltration, lymph node metastasis and the stages in lung invasive adenocarcinoma.Ki-67 expression was significantly positively correlated with VEGF and EGFR（P〈0.05）. Conclusion The high expression of EGFR, VEGF and Ki-67 may serve as the parameters for diagnosis of lung adenocarcinoma and determing biological behavior and prognosis of lung cancer. The tumor size of 2 cm may serve as a parameter for diagnosis and determing biological behavior and prognosis of lung adenocarcinoma in situ.