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. 2020 Apr;31(4):517-524.
doi: 10.1016/j.annonc.2020.01.014. Epub 2020 Jan 24.

Genomic origin and EGFR-TKI treatments of pulmonary adenosquamous carcinoma

G Lin  1 , C Li  2 , P S Li  3 , W Z Fang  4 , H P Xu  1 , Y H Gong  3 , Z F Zhu  5 , Y Hu  6 , W H Liang  7 , Q Chu  8 , W Z Zhong  9 , L Wu  10 , H J Wang  11 , Z J Wang  12 , Z M Li  13 , J Lin  14 , Y F Guan  3 , X F Xia  3 , X Yi  3 , Q Miao  1 , B Wu  1 , K Jiang  1 , X B Zheng  1 , W F Zhu  15 , X L Zheng  1 , P S Huang  16 , W J Xiao  16 , D Hu  15 , L F Zhang  1 , X R Fan  1 , T S K Mok  17 , C Huang  1
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Free article

Genomic origin and EGFR-TKI treatments of pulmonary adenosquamous carcinoma

G Lin et al. Ann Oncol. 2020 Apr.
Free article

Abstract

Background: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial.

Patients and methods: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes.

Results: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2).

Conclusions: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

Keywords: EGFR; EGFR-TKI; adenosquamous carcinoma; clonal origin; genomic profile.

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Conflict of interest statement

Disclosure TSKM reports grants and personal fees from AstraZeneca, Roche/Genentech, Bristol-Myers Squibb, Boehringer Ingelheim, Novartis, Merck Sharp and Dohme, Pfizer, SFJ Pharmaceuticals, Clovis Oncology, and Taiho; personal fees from Eli Lilly, Merck Serono, Vertex, ACEA Biosciences, Oncogenex, Celgene, and Ignyta; an uncompensated relationship with geneDecode and Cirina; grants from Eisai; and ownership of stock in Samomics Ltd. The remaining authors declare no conflicts of interest.

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