CR-UK Laboratories, Imperial College London, Hammersmith Hospitals campus, London, United Kingdom.
J Thorac Oncol. 2010 Mar;5(3):314-9. doi: 10.1097/JTO.0b013e3181ce6604.
The best hope of cure for patients with non-small cell lung cancer (NSCLC) is surgical resection. However, even in stage IA patients, 30% die within 5 years. Further improvements in survival require a biomarker(s), which defines the subset of these patients destined to do badly so that they could be targeted for additional therapies. Here, we investigate whether the immunohistochemical expression of a key kinase implicated in lung cancer biology, the mammalian target of rapamycin (mTOR) can predict survival outcome in patients with early stage resected NSCLC.
One hundred thirty-four patients with resected early stage (IA-IIB) NSCLC were pathologically reviewed centrally before staining for mTOR. Multiple variables including age, sex, stage, angioinvasion, lymph node status, and mTOR staining were assessed by univariate and multivariate analyses.
Stage (p = 0.044), lymph node status (p = 0.049), angioinvasion (p = 0.017), and mTOR staining (p = 0.007) were significant univariate predictors of poor survival. However, only angioinvasion (p = 0.016) and mTOR staining (p = 0.046) remained significant after multivariate analysis. Moreover, mTOR staining was the only variable to predict poor outcome in patients who either had negative lymph nodes (p = 0.016) or were stage IA (p = 0.0016).
The mTOR staining provides a new biomarker for poor outcome in early stage NSCLC and could enable resected stage IA patients to be selected for novel therapies possibly with an mTOR inhibitor.
非小细胞肺癌(NSCLC)患者的最佳治愈希望是手术切除。然而,即使在IA 期患者中,仍有 30%的患者在 5 年内死亡。要进一步提高生存率,就需要一个生物标志物,该标志物可以定义这些患者中预后不良的亚组,以便针对他们进行额外的治疗。在这里,我们研究了哺乳动物雷帕霉素靶蛋白(mTOR)在肺癌生物学中所涉及的关键激酶的免疫组化表达是否可以预测早期切除的 NSCLC 患者的生存结果。
对 134 例经病理复查确诊为早期(IA-IIB)NSCLC 的患者进行了 mTOR 染色。通过单变量和多变量分析评估了包括年龄、性别、分期、血管侵犯、淋巴结状态和 mTOR 染色在内的多个变量。
分期(p=0.044)、淋巴结状态(p=0.049)、血管侵犯(p=0.017)和 mTOR 染色(p=0.007)是单变量分析中不良生存的显著预测因素。然而,多变量分析后只有血管侵犯(p=0.016)和 mTOR 染色(p=0.046)仍然具有显著意义。此外,mTOR 染色是预测淋巴结阴性(p=0.016)或 IA 期(p=0.0016)患者预后不良的唯一变量。
mTOR 染色为早期 NSCLC 患者提供了一个新的不良预后生物标志物,并且可能使 IA 期患者能够选择接受新型治疗方法,包括可能使用 mTOR 抑制剂。