Boldrini Laura, Alì Greta, Gisfredi Silvia, Ursino Silvia, Baldini Editta, Melfi Franca, Lucchi Marco, Comin Camilla E, Maddau Cristina, Tibaldi Carmelo, Camacci Tiziano, Servadio Adele, Mussi Alfredo, Fontanini Gabriella
Department of Surgery, University of Pisa, Pisa, Italy.
Oncol Rep. 2009 Oct;22(4):683-91. doi: 10.3892/or_00000488.
Targeting the epidermal growth factor receptor has played a central role in advanced non-small cell lung cancer research, treatment, and patient outcomes over the last several years; however, a number of questions about this approach remain to be addressed. Through the Istituto Toscano Tumori and the Italian Association of Women Against Lung Cancer Project, we collected 411 lung adenocarcinomas from several clinical centers in Tuscany. Mutations were assessed by sequencing exons 18-21 of the epidermal growth factor receptor gene, and by restriction fragment length polymorphism analysis of codons 12 and 13 of the K-RAS gene. Epidermal growth factor receptor mutations (12.6%) were more frequently observed in females (p<0.0001), in non-smokers (p=0.005), and in the presence of bronchioloalveolar features (p=0.0004). K-RAS mutations (17.9%) were more frequent in males (p=0.0007) and were associated with smoking habits (p=0.005). Epidermal growth factor receptor and K-RAS mutations were mutually exclusive (p=0.001). We focused on 21 female patients with advanced/metastatic lung adenocarcinoma who received gefitinib 250 mg/day (expanded access) or erlotinib 150 mg/die as second/third-line therapy; partial response was associated with classic epidermal growth factor receptor mutations (p=0.006) and with a non-smoking history (p=0.02). None of the female patients with partial response and/or stable disease showed K-RAS alterations. Although the data obtained in our study have yet to be analyzed and confirmed with a larger number of patients treated with tyrosine kinase inhibitors, they should provide useful information for targeted therapy, in particular for non-smoking female lung cancer patients.
在过去几年中，针对表皮生长因子受体的研究在晚期非小细胞肺癌的研究、治疗及患者预后方面发挥了核心作用；然而，关于这种方法仍有一些问题有待解决。通过托斯卡纳肿瘤研究所和意大利女性抗肺癌协会项目，我们从托斯卡纳的多个临床中心收集了411例肺腺癌病例。通过对表皮生长因子受体基因的第18 - 21外显子进行测序，以及对K-RAS基因的第12和13密码子进行限制性片段长度多态性分析来评估突变情况。表皮生长因子受体突变（12.6%）在女性中更常见（p<0.0001）、在非吸烟者中更常见（p = 0.005）以及在具有细支气管肺泡特征时更常见（p = 0.0004）。K-RAS突变（17.9%）在男性中更常见（p = 0.0007）且与吸烟习惯相关（p = 0.005）。表皮生长因子受体和K-RAS突变相互排斥（p = 0.001）。我们重点关注了21例晚期/转移性肺腺癌女性患者，她们接受吉非替尼250毫克/天（扩大准入）或厄洛替尼150毫克/天作为二线/三线治疗；部分缓解与典型的表皮生长因子受体突变相关（p = 0.006）以及与无吸烟史相关（p = 0.02）。部分缓解和/或病情稳定的女性患者均未显示K-RAS改变。尽管我们研究中获得的数据尚未用大量接受酪氨酸激酶抑制剂治疗的患者进行分析和确认，但它们应为靶向治疗提供有用信息，特别是对于不吸烟的女性肺癌患者。
