Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, Japan.
Pangaea Oncology, Laboratory of Molecular Biology, Quirón-Dexeus University Institute, Barcelona, Spain.
J Cancer Res Clin Oncol. 2021 Dec;147(12):3709-3718. doi: 10.1007/s00432-021-03609-3. Epub 2021 Apr 1.
The clinicopathological or genetic features related to the prognosis of mucinous adenocarcinoma are unknown because of its rarity. The clinicopathological or targetable features were investigated for better management of patients with mucinous adenocarcinoma of the lung.
We comprehensively evaluated the clinicopathological and genetic features of 60 completely resected mucinous lung adenocarcinomas. Targetable genetic variants were explored using nCounter and polymerase chain reaction, PD-L1 and TTF-1 expression were evaluated using immunohistochemistry. We analyzed the prognostic impact using the Kaplan-Meier method and log-rank test.
Of the 60 enrolled patients, 13 (21.7%) had adenocarcinoma in situ/minimally invasive adenocarcinoma, and 47 (78.3%) had invasive mucinous adenocarcinoma (IMA). Fifteen patients (25%) showed a pneumonic appearance on computed tomography (CT). CD74-NRG1 fusion, EGFR mutations, and BRAF mutation were detected in three (5%), four (6.7%), and one (1.7%) patient(s), respectively. KRAS mutations were detected in 31 patients (51.7%). Two patients (3.5%) showed immunoreactivity for PD-L1. No in situ or minimally invasive cases recurred. IMA patients with pneumonic appearance had significantly worse recurrence-free survival (RFS) and overall survival (OS) (p < 0.001). Furthermore, IMA patients harboring KRAS mutations had worse RFS (p = 0.211). Multivariate analysis revealed that radiological pneumonic appearance was significantly associated with lower RFS (p < 0.003) and OS (p = 0.012). KRAS mutations served as an unfavorable status for RFS (p = 0.043).
Mucinous adenocarcinoma had a low frequency of targetable genetic variants and PD-L1 immunoreactivity; however, KRAS mutations were frequent. Pneumonic appearance on CT imaging and KRAS mutations were clinicopathological features associated with a worse prognosis.
由于黏液性腺癌较为罕见，其与预后相关的临床病理或遗传特征尚不清楚。本研究旨在调查黏液性腺癌的临床病理和可靶向特征，以更好地管理肺黏液性腺癌患者。
我们全面评估了 60 例完全切除的黏液性肺腺癌患者的临床病理和遗传特征。使用 nCounter 和聚合酶链反应（PCR）探索可靶向的遗传变异，使用免疫组织化学评估 PD-L1 和 TTF-1 的表达。我们使用 Kaplan-Meier 方法和对数秩检验分析预后影响。
在纳入的 60 例患者中，13 例（21.7%）为原位癌/微浸润性腺癌，47 例（78.3%）为浸润性黏液性腺癌（IMA）。15 例（25%）患者 CT 表现为肺炎样外观。3 例（5%）、4 例（6.7%）和 1 例（1.7%）患者检测到 CD74-NRG1 融合、EGFR 突变和 BRAF 突变。31 例（51.7%）患者检测到 KRAS 突变。2 例（3.5%）患者 PD-L1 免疫反应阳性。无原位或微浸润病例复发。具有肺炎样外观的 IMA 患者的无复发生存率（RFS）和总生存率（OS）显著更差（p<0.001）。此外，携带 KRAS 突变的 IMA 患者的 RFS 更差（p=0.211）。多因素分析显示，影像学肺炎样外观与较低的 RFS（p<0.003）和 OS（p=0.012）显著相关。KRAS 突变是 RFS 不良预后的因素（p=0.043）。
黏液性腺癌靶向治疗相关的遗传变异和 PD-L1 免疫反应频率较低，但 KRAS 突变较为常见。CT 成像上的肺炎样表现和 KRAS 突变是与预后较差相关的临床病理特征。
