EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry.
EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry.
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DOI：
10.1309/ajcpst1cthzs3psz
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发表时间：
2010-06
影响因子：
3.5
通讯作者：
Lindeman NI
中科院分区：
文献类型：
--
作者：
Sholl LM;Xiao Y;Joshi V;Yeap BY;Cioffredi LA;Jackman DM;Lee C;Jänne PA;Lindeman NI
约10%的非小细胞肺癌（NSCLC）患者对表皮生长因子受体（EGFR）靶向酪氨酸激酶抑制剂（TKI）有反应。超过75%的“应答者”具有EGFR激活突变。然而，突变分析并没有广泛使用，并且提出的替代方法（原位杂交和免疫组织化学分析）显示与结果不一致。本研究对40例接受TKI治疗的NSCLC患者的样本进行了荧光原位杂交（FISH）、显色原位杂交（CISH）、免疫组化分析和DNA测序。EGFR突变型肿瘤19例中有12例缓解，EGFR野生型肿瘤20例中有1例缓解（P = 0.0001），FISH+肿瘤19例中有7例缓解，FISH-肿瘤17例中有4例缓解（无显著性[NS]），CISH+肿瘤16例中有5例缓解，CISH-肿瘤21例中有6例缓解（NS），化学染色阳性肿瘤9例中有3例缓解，化学染色阴性肿瘤22例中有7例缓解（NS）。EGFR突变与无进展生存期的改善相关（P = 0.0004）。增加拷贝数（FISH或CISH）和蛋白表达（免疫组化）并不能独立预测结果。因此，EGFR序列分析是预测NSCLC患者TKI治疗后缓解和无进展生存期的唯一有效方法。
About 10% of patients with non–small cell lung carcinoma (NSCLC) respond to epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs). More than 75% of “responders” have activating mutations in EGFR. However, mutation analysis is not widely available, and proposed alternatives (in situ hybridization and immunohistochemical analysis) have shown inconsistent associations with outcome. Fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), immunohistochemical analysis, and DNA sequencing were compared in this study of 40 NSCLC samples from TKI-treated patients. Response rates were 12 of 19 in EGFR-mutant vs 1 of 20 EGFR wild-type tumors (P = .0001), 7 of 19 FISH+ vs 4 of 17 FISH– tumors (not significant [NS]), 5 of 16 CISH+ vs 6 of 21 CISH– tumors (NS), and 3 of 9 immunohistochemically positive vs 7 of 22 immunohistochemically negative tumors (NS). EGFR mutation was associated with improved progression-free survival (P = .0004). Increased copy number (FISH or CISH) and protein expression (immunohistochemical) did not independently predict outcome. Thus, EGFR sequence analysis was the only method useful for predicting response and progression-free survival following TKI therapy in NSCLC.