肺腺癌脑转移病理学特征及人类间变性淋巴瘤激酶和表皮生长因子受体诊断价值

Histopathological features with anaplastic lymphoma kinase and epidermal growth factor receptor expression of brain metastases from lung adenocarcinoma

目的总结肺腺癌脑转移的病理学特征,并探讨人类间变性淋巴瘤激酶(ALK)和表皮生长因子受体(EGFR)的诊断价值。方法收集2013年1月至2016年12月在复旦大学附属华山医院神经外科手术切取的86例非小细胞肺癌脑转移的脑组织标本,经HE染色和免疫组化染色进行病理学分析,经免疫组化染色检测ALK和EGFR阳性率。结果 86例非小细胞肺癌患者中74例(86.05%)发生肺腺癌脑转移,其病理分型为实体型44例(59.46%)、腺泡型9例(12.16%)、乳头型14例(18.42%)和微乳头型7例(9.46%),与文献报道的原发性肺腺癌的病理分型差异有统计学意义(χ^(2)=97.858,P=0.000)。肺腺癌脑转移ALK阳性率为9.46%(7/74),不同病理分型差异无统计学意义(χ^(2)=1.690,P=0.639);EGFR阳性率为52.70%(39/74),不同病理分型差异有统计学意义(χ^(2)=7.938,P=0.047);突变型EGFR总体阳性率为33.78%(25/74),不同病理分型差异无统计学意义(χ^(2)=1.721,P=0.632),其中EGFR-19阳性率为18.92%(14/74)、EGFR-21为16.22%(12/74)。肺腺癌脑转移患者ALK与EGFR的表达可能存在相互排斥(χ^(2)=12.462,P=0.001)。结论肺腺癌实体型和微乳头型具有较高的脑转移率。肺腺癌脑转移ALK和EGFR表达与原发性肺腺癌相一致,且二者表达可能存在相互排斥。

Objective To analyze the clinical-pathological features of brain metastases of lung adenocarcinoma and detect the expressions of anaplastic lymphoma kinase(ALK) and epidermal growth factor receptor(EGFR) in order to guide the targeted drug therapy of patients with advanced lung cancer.M ethodsA total of 86 cases of brain metastases from non-small cell lung cancer(NSCLC) in Huashan Hospital, Fudan University from January 2013 to December 2016 were selected for pathological analysis by HE staining and immunolabeling, ALK and EGFR expression were detected by immunohistochemical staining.Results Among 86 cases of brain metastases from NSCLC, 74 cases(86.05%) were adenocarcinoma, 3 cases(3.49%) of squamous cell carcinoma, and 9 cases(10.47%) of neuroendocrine tumors. Among the 74 brain metastases from lung adenocarcinoma, there were 44 cases(59.46%) of solid type, 9 cases(12.16%) of acinar type, 14 cases(18.42%) of papillary type and 7 cases(9.46%) of micropapillary type, which were significantly different from the pathological subtypes of primary lung adenocarcinoma reported in the literature(χ^(2)= 97.858, P = 0.000). The expression rate of ALK protein was9.46%(7/74), the expression rates were not statistically significant in different pathological types(χ^(2)=1.690, P = 0.639). The expression rate of EGFR non-mutant protein was 52.70%(39/74), and the expression rates were statistically significant in different pathological types(χ^(2)= 7.938, P = 0.047). Fourteen cases(18.92%, 14/74) showed positive staining by specific mutation antibody of exon 19 of EGFR gene,while 12 cases(16.22%, 12/74) having exon 21 of EGFR gene mutation, and the total positive rate was33.78%(25/74), the expression rates were not statistically significant in different pathological types(χ^(2)=1.721, P = 0.632). The expression levels of ALK and EGFR in brain metastases from lung adenocarcinoma were mutually exclusive(χ^(2)= 12.462, P = 0.001).Conclusions Among lung adenocarcinoma, the solid lung type and the micropapillary type have higher tendencies of brain metastasis. The expression rates of ALK and EGFR in brain metastases were consistent with those of primary lung adenocarcinoma, and their expression was mutually exclusive.