Dumenil Coraline, Vieira Thibault, Rouleau Etienne, Antoine Martine, Duruisseaux Michael, Poulot Virginie, Lacave Roger, Cadranel Jacques, Massiani Marie-Ange, Wislez Marie
Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France.
Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France; GRC-UPMC 04 Theranoscan, Université Paris 6 Pierre et Marie Curie, 4 place Jussieu, 75252 Paris, France.
Lung Cancer. 2015 Dec;90(3):561-7. doi: 10.1016/j.lungcan.2015.10.012. Epub 2015 Oct 14.
KRAS mutations occur in 20 to 25% of non-small-cell lung cancers (NSCLC) and seem to predict a poor prognosis. There is heterogeneousness in the frequency and spectrum of KRAS mutations, which can be categorized in transitions and transversions. We wondered if subtypes of KRAS mutation were associated with specific clinical phenotypes and specific survival.
Between July 2007 and May 2012, patients with advanced NSCLC and KRAS mutation diagnosed in two university hospitals were included. Clinical and histological characteristics, therapeutics and survival data were collected.
Among 635 patients screened for KRAS mutations, 90 were found to be mutated and were included. Median age was 59 years (range: 54-69). Most were males (60%), current or former smokers (63% and 33%, respectively) and had an adenocarcinoma (ADC) (80%). Eighty patients were stage IV and 10 were stage IIIB. Eighty percent of the KRAS mutations were transversions and 20% were transitions. In uni- and multivariate analyses, there was a trend for fewer smokers among patients with transitions than among those with transversions (Odds Ratio [OR]=0.28, 95% CI [0.079-0.999], p=0.05). No significant difference was noted between transitions and transversions for other clinical characteristics. Patients with transitions had more frequently squamous-cell carcinoma (SCC) compared to those with transversions, who had more frequently adenocarcinomas (OR=16.7, 95% CI [2.76-100.8], p=0.002). Seventy-nine patients (86%) had received first-line chemotherapy. No significant difference was seen for disease-control rate, median progression-free survival or overall survival between transitions and transversions.
A higher proportion of non-smokers and SCC subtypes were observed in the transitions compared to transversions. This confirms the heterogeneity of KRAS mutations and could suggest to expand KRAS testing in SCC to assess impact of RAS in SCC, which remains poorly investigated.
KRAS 突变发生于 20%至 25%的非小细胞肺癌（NSCLC）中，且似乎预示着预后不良。KRAS 突变的频率和谱存在异质性，可分为转换和颠换。我们想知道 KRAS 突变亚型是否与特定临床表型及特定生存情况相关。
纳入 2007 年 7 月至 2012 年 5 月期间在两家大学医院确诊为晚期 NSCLC 且存在 KRAS 突变的患者。收集临床和组织学特征、治疗方法及生存数据。
在 635 例接受 KRAS 突变筛查的患者中，90 例被发现存在突变并被纳入研究。中位年龄为 59 岁（范围：54 - 69 岁）。大多数为男性（60%），目前或既往吸烟者分别占 63%和 33%，且患有腺癌（ADC）的占 80%。80 例患者为 IV 期，10 例为 IIIB 期。80%的 KRAS 突变为颠换，20%为转换。在单因素和多因素分析中，转换型患者中的吸烟者比颠换型患者少，存在这种趋势（比值比[OR]=0.28，95%置信区间[CI][0.079 - 0.999]，p = 0.05）。其他临床特征在转换型和颠换型之间未观察到显著差异。与颠换型患者相比，转换型患者更常发生鳞状细胞癌（SCC），而颠换型患者更常发生腺癌（OR = 16.7，95% CI[2.76 - 100.8]，p = 0.002）。79 例患者（86%）接受了一线化疗。转换型和颠换型在疾病控制率、中位无进展生存期或总生存期方面未观察到显著差异。
与颠换型相比，转换型中观察到非吸烟者和 SCC 亚型的比例更高。这证实了 KRAS 突变的异质性，并可能提示扩大 SCC 中 KRAS 检测以评估 RAS 在 SCC 中的影响，目前 SCC 方面的研究仍较少。
