Central Laboratory, The First People's Hospital of Huzhou, No. 158 Guangchang Back Road, Huzhou, 313000, Zhejiang, People's Republic of China.
Department of Cardiothoracic Surgery, The First People's Hospital of Huzhou, Huzhou, 313000, People's Republic of China.
World J Surg Oncol. 2020 Jul 16;18(1):172. doi: 10.1186/s12957-020-01947-z.
Several genetic driver alterations have been identified in micropapillary lung adenocarcinoma (MPA). However, the frequency of co-alteration of ROS1, EGFR, and EML4-ALK is yet unclear. Herein, we investigated the relationship between clinicopathologic characteristics and well-identified driver mutations of MPA compared with non-micropapillary lung adenocarcinoma (LA).
Formalin-fixed paraffin-embedded (FFPE) sections derived from lung adenocarcinoma patients who never received adjuvant chemotherapy or radiation therapy prior to surgical resection were collected from October 2016 to June 2019. EGFR mutations, ROS1 rearrangements, and EML4-ALK fusion were identified in a set of 131 MPA and LA cases by using the amplification refractory mutation system (ARMS). The response rate and duration of response were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
EGFR mutations had occurred in 42 (76.4%) MPA patients and 42 (55.3%) LA patients. Interestingly, ROS1 rearrangements were highly enriched only in the MPA cases (6/55, 10.9%) but rarely in the LA cases (1/76, 1.3%). Furthermore, 7.3% (4/55) MPA samples had double gene mutations, while only 1.3% (1/76) LA cases had double gene alterations. Of 5 patients with harboring two driver oncogene mutations, four patients (80%) obtained partial response, and one patient (20%) suffered recurrence.
A higher prevalence of ROS1 rearrangement or combined mutations of ROS1, EGFR, and EML4-ALK may play a critical role in the tumorigenesis of MPA. These findings provide a novel therapeutic strategy for patients with malignant MPA through combining TKIs than one TKI.
微乳头型肺腺癌（MPA）中已鉴定出几种遗传驱动改变。然而，ROS1、EGFR 和 EML4-ALK 共改变的频率尚不清楚。在此，我们研究了 MPA 与非微乳头肺腺癌（LA）相比，临床病理特征与明确的驱动突变之间的关系。
从 2016 年 10 月至 2019 年 6 月，收集了从未接受过辅助化疗或放疗的肺腺癌患者的福尔马林固定石蜡包埋（FFPE）切片。通过扩增不可阻挡突变系统（ARMS）在一组 131 例 MPA 和 LA 病例中鉴定 EGFR 突变、ROS1 重排和 EML4-ALK 融合。使用实体瘤反应评估标准 1.1（RECIST 1.1）评估反应率和反应持续时间。
EGFR 突变发生在 42（76.4%）例 MPA 患者和 42（55.3%）例 LA 患者中。有趣的是，ROS1 重排仅在 MPA 病例中高度富集（6/55，10.9%），而在 LA 病例中很少见（1/76，1.3%）。此外，7.3%（4/55）的 MPA 样本有双基因突变，而只有 1.3%（1/76）的 LA 病例有双基因突变改变。在携带两种驱动致癌基因突变的 5 名患者中，4 名患者（80%）获得部分缓解，1 名患者（20%）复发。
ROS1 重排或 ROS1、EGFR 和 EML4-ALK 联合突变的更高发生率可能在 MPA 的肿瘤发生中起关键作用。这些发现为恶性 MPA 患者提供了一种新的治疗策略，即通过联合 TKI 而不是一种 TKI 来治疗。
