*Thoracic Surgery Unit ∥Institute of Pathological Anatomy and Histology, University of Perugia Medical School †Medical Oncology Division, S. Maria della Misericordia Hospital ‡Department of Electronic and Information Engineering, University of Perugia, Perugia §Thoracic Surgery Unit, S. Camillo Forlanini Hospital, Roma, Italy.
Am J Clin Oncol. 2014 Aug;37(4):343-9. doi: 10.1097/COC.0b013e31827a7e7a.
Surgery yields best results for non-small cell lung cancer (NSCLC) patients. Epidermal growth factor receptor (EGFR) and its downstream factor Kirsten rat sarcoma viral oncogene homolog (KRAS) are variably mutated in NSCLC. Such mutations predict clinical response to tyrosine kinase inhibitors. This study evaluated incidence and correlation of EGFR and KRAS mutations with clinicopathologic parameters and outcome in resected stage I to III NSCLC.
We analyzed the clinical characteristics and outcome data for 230 patients who underwent resection at our institution for stage I to III NSCLC. The tumors were assessed for both EGFR (exons 18 to 21) and KRAS (exons 2 and 3) mutations by nested polymerase chain reaction and sequenced in both sense and antisense direction. Kaplan-Meier estimates of overall survival and disease-free survival were calculated for clinical and biological variables using Cox model.
EGFR and KRAS mutations were detected in 22 (9.6%) and 39 (16.9%) patients, respectively. In the whole population, both EGFR and KRAS mutations were significantly correlated with adenocarcinoma (ADC). Overall, EGFR mutations were more frequent in women (P<0.0001) and in nonsmokers (P<0.0001). In the ADC/BAC group, KRAS mutations were more frequent in man (P<0.02) and EGFR mutations (exon 19 deletion and L858R) demonstrated a tendency towards worse disease-free survival (P=0.056). No difference in outcome was seen between patients harboring KRAS mutations compared with KRAS wild type.
EGFR and KRAS mutations are frequent in ADCs and are not prognostic factors for survival. EGFR mutations could be used to identify patients suitable for adjuvant treatment with targeted therapy resulting in potentially improved outcomes.
手术是治疗非小细胞肺癌（NSCLC）患者的最佳方法。表皮生长因子受体（EGFR）及其下游因子 Kirsten 大鼠肉瘤病毒致癌基因同源物（KRAS）在 NSCLC 中存在不同程度的突变。这些突变预测酪氨酸激酶抑制剂的临床反应。本研究评估了 EGFR 和 KRAS 突变与 NSCLC Ⅰ期至Ⅲ期切除患者的临床病理参数和预后的相关性。
我们分析了在我院接受Ⅰ期至Ⅲ期 NSCLC 切除术的 230 例患者的临床特征和预后数据。通过巢式聚合酶链反应检测肿瘤的 EGFR（外显子 18 至 21）和 KRAS（外显子 2 和 3）突变，并进行正反双向测序。采用 Cox 模型计算临床和生物学变量对总生存和无病生存的 Kaplan-Meier 估计。
分别在 22 例（9.6%）和 39 例（16.9%）患者中检测到 EGFR 和 KRAS 突变。在全人群中，EGFR 和 KRAS 突变均与腺癌（ADC）显著相关。总体而言，EGFR 突变在女性中更为常见（P<0.0001），在非吸烟者中更为常见（P<0.0001）。在 ADC/BAC 组中，KRAS 突变在男性中更为常见（P<0.02），EGFR 突变（外显子 19 缺失和 L858R）显示出无病生存较差的趋势（P=0.056）。与 KRAS 野生型相比，携带 KRAS 突变的患者的预后无差异。
EGFR 和 KRAS 突变在 ADC 中较为常见，不是生存的预后因素。EGFR 突变可用于识别适合辅助治疗的患者，从而可能改善预后。
