Oncogenic mutations are associated with histological subtypes but do not have an independent prognostic value in lung adenocarcinoma
Oncogenic mutations are associated with histological subtypes but do not have an independent prognostic value in lung adenocarcinoma
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致癌突变与组织学亚型相关，但在肺腺癌中没有独立的预后价值
DOI：
10.2147/ott.s58900
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Chen, Haiquan
中科院分区：
文献类型：
--
作者：
Hu, Haichuan;Pan, Yunjian;Chen, Haiquan
肺腺癌具有不同的遗传和形态学背景，通常根据其独特的致癌突变（或所谓的驱动突变）和组织学亚型（国际肺癌研究协会/美国胸科学会/欧洲呼吸学会[IASLC/ATS/ERS]提出的从头分类）进行分类。尽管这两种分类对于个性化治疗至关重要，但它们的综合临床效果仍不清楚。因此，我们分析了 981 例肺腺癌，以检测致癌突变和组织学亚型对预后的潜在相关性和综合影响。致癌突变分析包括直接测序 EGFR、KRAS、HER2、BRAF、PIK3CA、ALK 和 RET 的致癌突变/重排，并对 IASLC/ATS/ERS 分类进行重新审查。符合条件的肿瘤包括 13 例非典型腺瘤性增生/原位腺癌、20 例微浸润腺癌、901 例浸润性腺癌、44 例浸润性粘液性腺癌和其他 3 种变体。与侵袭性腺癌相比，侵袭性粘液腺癌的 EGFR 突变患病率较低，但 KRAS、ALK 和 HER2 突变的患病率较高。吸烟、固体为主模式和粘液成分与较少的 EGFR 突变独立相关。 ALK 重排在具有少量粘液成分的肿瘤中更常见，而 KRAS 突变在吸烟者中更常见。此外，还对 503 名 I-IIIA 期肿瘤患者的总生存期 (OS) 和无复发生存期进行了分析。分期和组织学模式是无复发生存的独立预测因子，病理分期是 OS 的唯一独立预测因子。尽管携带 EGFR 突变的患者比没有携带突变的患者有更好的 OS，但没有致癌突变是生存的独立预测因素。致癌突变与新的 IASLC/ATS/ERS 分类相关，这有利于基于形态学的突变分析策略。这两种分类的结合可能不会增加预后能力，但它为个性化治疗提供了必要的信息。
Lung adenocarcinomas have diverse genetic and morphological backgrounds and are usually classified according to their distinct oncogenic mutations (or so-called driver mutations) and histological subtypes (the de novo classification proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society [IASLC/ATS/ERS]). Although both these classifications are essential for personalized treatment, their integrated clinical effect remains unclear. Therefore, we analyzed 981 lung adenocarcinomas to detect the potential correlation and combined effect of oncogenic mutations and histological subtype on prognosis. Analysis for oncogenic mutations included the direct sequencing of EGFR, KRAS, HER2, BRAF, PIK3CA, ALK, and RET for oncogenic mutations/rearrangements, and a rereview of the IASLC/ATS/ERS classification was undertaken. Eligible tumors included 13 atypical adenomatous hyperplasia/adenocarcinoma in situ, 20 minimally invasive adenocarcinomas, 901 invasive adenocarcinomas, 44 invasive mucinous adenocarcinomas, and three other variants. The invasive mucinous adenocarcinomas had a lower prevalence of EGFR mutations but a higher prevalence of KRAS, ALK, and HER2 mutations than invasive adenocarcinomas. Smoking, a solid predominant pattern, and a mucinous component were independently associated with fewer EGFR mutations. The ALK rearrangements were more frequently observed in tumors with a minor mucinous component, while the KRAS mutations were more prevalent in smokers. In addition, 503 patients with stage I-IIIA tumors were analyzed for overall survival (OS) and relapse-free survival. The stage and histological pattern were independent predictors of relapse-free survival, and the pathological stage was the only independent predictor for the OS. Although patients with the EGFR mutations had better OS than those without the mutations, no oncogenic mutation was an independent predictor of survival. Oncogenic mutations were associated with the novel IASLC/ATS/ERS classification, which facilitates a morphology-based mutational analysis strategy. The combination of these two classifications might not increase the prognostic ability, but it provides essential information for personalized treatment.