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. 2020 Jul 16;18(1):172.
doi: 10.1186/s12957-020-01947-z.

A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

Xilin Zhang  1 , Yan Jiang  1 , Huanming Yu  2 , Hui Xia  3 , Xiang Wang  4
Affiliations

A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

Xilin Zhang et al. World J Surg Oncol. .

Abstract

Background: 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).

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: EGFR; EML4-ALK; Lung adenocarcinoma; Micropapillary pattern; ROS1.

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Conflict of interest statement

All authors declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig. 1
Fig. 1
Immunohistochemical staining and mutation analysis of MPA and LA patients. Three micrometers FFPE sections of MPA (patient 1) and LA (patient 16) were immunostained with hematoxylin and eosin (× 100 magnification). Scale bar 20 μm. Abbreviations: MPA, micropapillary lung adenocarcinoma; LA, lung adenocarcinoma without micropapillary component
See this image and copyright information in PMC

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