High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma: A population-based single-institution study
High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma: A population-based single-institution study
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DOI：
10.1016/j.neo.2020.05.004
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发表时间：
2020-09-01
期刊：
影响因子：
4.8
通讯作者：
Taimen, Pekka
中科院分区：
文献类型：
--
作者：
Talvitie, Eva-Maria;Vilhonen, Heikki;Taimen, Pekka
目的：肿瘤突变负荷（TMB）是一种新兴的预测癌症的生物标志物。很少有研究讨论TMB在非小细胞肺癌中的预后作用，结果相互矛盾。此外，TMB与肺腺癌不同组织学亚型的相关性迄今尚未得到系统评价。在这里，我们研究了TMB的预后价值和它的分布在不同的组织学亚型的肺腺癌在一个回顾性队列使用最新更新的classification guidelines.Materials and Methods：176例手术切除的I-IV期肺腺癌根据WHO 2015年指南进行组织学重新分类。进一步应用了将腺泡亚型细分为经典腺泡、复杂腺泡和筛状亚型的改良分类，并评价了潜在的预后组织病理学特征，如肿瘤浸润淋巴细胞。148例I-III期肿瘤患者和完整的随访数据被纳入生存分析。TMB是由商业下一代测序面板从131个肿瘤，其中105个有生存databasesavailable.Results：占主导地位的微乳头状，固体和复杂的腺以及非主导筛状组织学亚型与生存期显着缩短。高TMB集中在微乳头，实性和腺泡为主的亚型。有趣的是，在多变量分析中，与TMB < 14相比，TMB >= 14突变/MB赋予了分期和组织学独立的生存益处，（HR 0.284，95% CI 0.14-0.59，P=0.001）和疾病特异性生存期结论：TMB是肺腺癌预后良好的独立生物标志物，尽管其与肺腺癌的主要组织学亚型相关，但仍被认为是侵袭性的。
Objectives: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines.Materials and methods: 176 surgically resected stage I-IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I-III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available.Results: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB >= 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14-0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08-0.56, P=0.002).Conclusion: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.