Dziadziuszko R, Holm B, Skov B G, Osterlind K, Sellers M V, Franklin W A, Bunn P A, Varella-Garcia M, Hirsch F R
University of Colorado Health Sciences Center, Aurora, CO, USA.
Ann Oncol. 2007 Mar;18(3):447-52. doi: 10.1093/annonc/mdl407. Epub 2006 Nov 2.
Survival benefit of non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is predicted by high EGFR gene copy number and by strong EGFR protein expression. Clinical relevance of these features in patients treated with chemotherapy has not been reported.
This study included 82 NSCLC patients treated with chemotherapy. There were 45% of females, 6% of never smokers and 45% of patients diagnosed with adenocarcinoma. EGFR gene copy number was evaluated by fluorescence in situ hybridization and EGFR protein level by immunohistochemistry.
High EGFR gene copy number and protein level were found in 33% and 71% of patients, respectively. Both markers were significantly associated (P = 0.01). For objective response and disease control, there was no difference between patients defined as negative or positive for both EGFR gene copy number (P = 0.39 and P = 1.00, respectively) and for EGFR protein (P = 1.00 and P = 0.80, respectively). There were no differences in progression-free and overall survival according to EGFR gene copy number (P = 0.76 and P = 0.82, respectively) and protein level (P = 0.67 and P = 0.62, respectively).
In chemotherapy-treated NSCLC patients, EGFR gene copy number was positively associated with protein level but none of the features were predictive for either treatment response or survival.
表皮生长因子受体(EGFR)酪氨酸激酶抑制剂治疗的非小细胞肺癌(NSCLC)患者的生存获益可通过高EGFR基因拷贝数和强EGFR蛋白表达来预测。这些特征在接受化疗的患者中的临床相关性尚未见报道。
本研究纳入82例接受化疗的NSCLC患者。其中女性占45%,从不吸烟者占6%,腺癌患者占45%。通过荧光原位杂交评估EGFR基因拷贝数,通过免疫组化评估EGFR蛋白水平。
分别在33%和71%的患者中发现高EGFR基因拷贝数和蛋白水平。两种标志物显著相关(P = 0.01)。对于客观缓解率和疾病控制率,EGFR基因拷贝数定义为阴性或阳性的患者之间无差异(分别为P = 0.39和P = 1.00),EGFR蛋白定义为阴性或阳性的患者之间也无差异(分别为P = 1.00和P = 0.80)。根据EGFR基因拷贝数(分别为P = 0.76和P = 0.82)和蛋白水平(分别为P = 0.67和P = 0.62),无进展生存期和总生存期无差异。
在接受化疗的NSCLC患者中,EGFR基因拷贝数与蛋白水平呈正相关,但这些特征均不能预测治疗反应或生存情况。