Correlation of Mutation Status and Survival with Predominant Histologic Subtype According to the New IASLC/ATS/ERS Lung Adenocarcinoma Classification in Stage III (N2) Patients
Correlation of Mutation Status and Survival with Predominant Histologic Subtype According to the New IASLC/ATS/ERS Lung Adenocarcinoma Classification in Stage III (N2) Patients
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DOI：
10.1097/jto.0b013e3182828fb8
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发表时间：
2013-04-01
影响因子：
20.4
通讯作者：
John, Thomas
中科院分区：
文献类型：
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作者：
Russell, Prudence A.;Barnett, Stephen A.;John, Thomas
导言：根据国际肺癌研究协会/美国胸科学会/欧洲呼吸学会国际多学科肺腺癌分类，我们调查了主要亚型、突变状态和III(N2)期肺腺癌患者预后之间的关系。方法：我们确定了1993至2011年间有治疗意图的69例III(N2)肺腺癌患者，这些患者有足够的肿瘤组织进行分子分析，并有足够的随访时间进行生存分析。提取DNA，用Sequenom‘s OncoCarta Panel(v1.0；Sequenom，San Diego，CA)进行突变检测。结果：大多数肿瘤为腺泡型(26/69，38%)、实体型(24/69，35%)和微乳头型(13/69，19%)。在59个肿瘤中，17个肿瘤(29%)和13个肿瘤(22%)发现了EGFR和KRAS突变。EGFR突变多见于腺泡型(11/25，占44%)和微乳头型肿瘤(5/13，占38%)(p=0.009)，而KRAS突变最常发生在实性占优势的肿瘤(9/21，占43%)(p=0.016)。腺泡占优势的肿瘤患者的总体存活率显著高于非腺泡占优势的患者(风险比：0.45；95%可信区间：0.22-0.91；p=0.026)，在调整了表皮生长因子受体的状态、T分期、性别和年龄后，这一结果仍然显著。EGFR突变的微乳头占优势的肿瘤患者的存活率与EGFR突变的腺泡占优势的肿瘤患者相似。结论：原发灶中的优势亚型与手术切除的III(N2)期肺腺癌的总体生存率有关，与突变状态无关。组织学分型提供了重要的预后信息和潜在的分子相关性。
Introduction: We investigated the relationship between predominant subtype, according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification; mutation status; and patient outcome in stage III (N2) lung adenocarcinoma.Methods: We identified 69 patients with stage III (N2) lung adenocarcinoma operated on with curative intent between 1993 and 2011 who had adequate tumor tissue for molecular analysis and adequate follow-up time for survival analysis. DNA was isolated and tested for mutations using Sequenom's OncoCarta Panel (v1.0; Sequenom, San Diego, CA).Results: The majority of tumors were acinar (26 of 69 tumors; 38%), solid (24 of 69 tumors; 35%), and micropapillary predominant (13 of 69 tumors; 19%) subtypes. EGFR and KRAS mutations were identified in 17 of 59 tumors (29%) and 13 of 59 tumors (22%), respectively. EGFR mutations occurred most often in acinar (11 of 25 tumors; 44%) and micropapillary predominant tumors (five of 13 tumors; 38%) (p = 0.009), whereas KRAS mutations occurred most often in solid predominant tumors (nine of 21 tumors; 43%) (p = 0.016). Patients with acinar predominant tumors had significantly improved overall survival compared with those with non-acinar predominant tumors (hazard ratio: 0.45; 95% confidence interval: 0.22-0.91; p = 0.026), which remained significant after adjustment for EGFR status, T-stage, sex, and age. Patients with EGFR-mutant micropapillary predominant tumors had similar survival to those with EGFR-mutant acinar predominant tumors. The predominant subtype in the primary tumor was most often seen in the N2 node in micropapillary and solid predominant tumors but not in acinar predominant tumors.Conclusions: The predominant subtype in the primary tumor was associated with overall survival in resected stage III (N2) lung adenocarcinoma and was independent of mutation status. Histologic subtyping provides important prognostic information and potentially molecular correlates.