新 IASLC/ATS/ERS 肺腺癌分类中 III 期（N2）患者主要组织学亚型与突变状态和生存的相关性。

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.

机构信息

Department of Anatomical Pathology, St Vincent's Hospital, The University of Melbourne, Melbourne, Australia.

出版信息

J Thorac Oncol. 2013 Apr;8(4):461-8. doi: 10.1097/JTO.0b013e3182828fb8.

DOI:10.1097/JTO.0b013e3182828fb8

PMID:23486266

Abstract

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.

摘要

介绍

我们研究了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的主要亚型、突变状态与 III 期（N2）肺腺癌患者预后之间的关系。

方法

我们共纳入 69 例 1993 年至 2011 年间接受以治愈为目的手术的 III 期（N2）肺腺癌患者，这些患者有足够的肿瘤组织进行分子分析和足够的随访时间进行生存分析。使用 Sequenom 的 OncoCarta 试剂盒（v1.0；Sequenom，圣地亚哥，CA）分离并检测 DNA 突变。

结果

大多数肿瘤为腺泡型（69 例肿瘤中的 26 例；38%）、实体型（69 例肿瘤中的 24 例；35%）和微乳头型为主（69 例肿瘤中的 13 例；19%）亚型。在 59 例肿瘤中发现了 17 例 EGFR 突变（29%）和 13 例 KRAS 突变（22%）。EGFR 突变最常发生于腺泡型（25 例肿瘤中的 11 例；44%）和微乳头型为主的肿瘤（13 例中的 5 例；38%）（p=0.009），而 KRAS 突变最常发生于实体型为主的肿瘤（21 例肿瘤中的 9 例；43%）（p=0.016）。腺泡型为主肿瘤患者的总生存明显优于非腺泡型为主肿瘤患者（风险比：0.45；95%置信区间：0.22-0.91；p=0.026），这一结果在调整 EGFR 状态、T 分期、性别和年龄后仍然显著。微乳头型为主且 EGFR 突变的肿瘤患者的生存情况与 EGFR 突变的腺泡型为主肿瘤患者相似。在微乳头型和实体型为主的肿瘤中，主要肿瘤的主要亚型最常出现在 N2 淋巴结中，但在腺泡型为主的肿瘤中则不然。