Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations.
Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations.
复制标题
NSCLC的综合分子分析；临床病理协会。
DOI：
10.1371/journal.pone.0133859
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Saetta AA
中科院分区：
文献类型：
--
作者：
Chatziandreou I;Tsioli P;Sakellariou S;Mourkioti I;Giannopoulou I;Levidou G;Korkolopoulou P;Patsouris E;Saetta AA
目前，选择NSCLC患者进行靶向治疗是基于EGFR和EML 4/ALK易位中存在致敏突变。肺癌分子变化的异质性导致人们不断发现潜在的生物标志物和靶点，以提高生存率。本研究旨在使用高灵敏度技术检测956例希腊NSCLC患者的EGFR、KRAS、BRAF、PIK 3CA、MET基因拷贝数和ALK重排的改变，并与临床病理特征进行相关性分析。EGFR突变检出率为10.6%（956个样本中的101个），KRAS 26.5%（720个样本中的191个），BRAF 2.5%（12/471份样本），PIK 3CA 3.8%（184个样本中的7个），18%（170个样本中的31个）检测到MET基因扩增，3.7%（107个样本中的4个）检测到ALK重排。EGFR突变在外显子19（61.4%的突变病例）、外显子21 p.Leu858Arg（19.8%）、外显子20（15.8%）、外显子18（2.9%）中检出，并与性别、组织学、吸烟状况和TTF 1染色相关。p.Thr790Met突变病例（3.9%）显示外显子19或21的同时突变。阴性TTF-1染色显示EGFR突变存在的强阴性预测值。KRAS突变与组织学相关，最常见的突变是p.Gly12Cys（38%）。总之，只有89例患者有资格接受EGFR-TKI和ALK抑制剂治疗，而257例患者显示出其他改变，这突出表明有必要进行详细的分子特征分析，从而可能为NSCLC患者提供更有效的个体化治疗。
Selection of NSCLC patients for targeted therapy is currently based upon the presence of sensitizing mutations in EGFR and EML4/ALK translocations. The heterogeneity of molecular alterations in lung cancer has led to the ongoing discovery of potential biomarkers and targets in order to improve survival. This study aimed to detect alterations in EGFR, KRAS, BRAF, PIK3CA, MET-gene copy number and ALK rearrangements in a large cohort of 956 NSCLC patients of Hellenic origin using highly sensitive techniques and correlations with clinicopathological characteristics. Mutations were detected in EGFR 10.6% (101 out of 956 samples), KRAS 26.5% (191 out of 720 samples), BRAF 2.5% (12 out of 471 samples), PIK3CA 3.8% (7 out of 184 samples), MET gene amplification was detected in 18% (31 out of 170) and ALK rearrangements in 3.7% (4 out of 107 samples). EGFR mutations were detected in exon 19 (61.4% of mutant cases), exon 21 p.Leu858Arg (19.8%), exon 20 (15.8%), exon 18 (2.9%) and were correlated with gender histology, smoking status and TTF1 staining. p.Thr790Met mutant cases (3.9%) displayed concurrent mutations in exons 19 or 21. Negative TTF-1 staining showed strong negative predictive value for the presence of EGFR mutations. KRAS mutations were associated with histology, the most common mutation being p.Gly12Cys (38%). In conclusion, only 89 patients were eligible for EGFR -TKIs and ALK inhibitors therapy, whereas 257 patients showed other alterations, highlighting the necessity for a detailed molecular profiling potentially leading to more efficient individualized therapies for NSCLC patients.
DOI：
10.4061/2011/312346
发表时间：
2011
期刊：
Pathology research international
影响因子：
--
作者：
Dimou A;Harrington K;Syrigos KN
通讯作者：
Syrigos KN