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Updated: Nov 29, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Genetic heterogeneity and predictive biomarker for pulmonary sarcomatoid carcinomas
Jing Qin1, Bo Chen2, Chenghui Li3
1Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (lung and esophagus), Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 310022, PR China; Department of Thoracic Medical Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 310022, PR China.
Purpose:
The aim of this study is to investigate the genetic heterogeneity (carcinomatous vs. sarcomatous components) and predictive biomarkers in patients with pulmonary sarcomatoid carcinoma (PSC).
Methods:
Genetic alterations and biomarkers of immunotherapy were performed in a discovery set (n = 6) of PSC. Next-generation sequencing (NGS) on a pan-cancer gene panel was applied to detect the genetic alterations in each component, and the respective mutation profiling and tumor mutation burden (TMB) were compared as well. Immunohistochemistry (IHC) assay with SP263 antibody was used to detect the protein expression of programmed death-ligand 1 (PD-L1) in each component.
Results:
Comparative genetic analysis revealed that the separate carcinomatous and sarcomatous components shared strikingly common mutations. TP53 (4/6, 66.7%) was the most common genetic alteration in 6 PSC patients. MET exon 14 skipping was detected in one case, accounting for 16.7%. An EZR-ROS1 fusion (EZR: intron10-ROS1: intron32) was identified in one case. The TMB of the two components was similar. Nevertheless, significantly higher PD-L1 expression was found in carcinomatous components compared to sarcomatous components. MDM2 amplification was detected in 2/6 (33.3%) of cases and STK11 mutation in 1/6 (16.7%) of cases.
Conclusions:
PSC containing carcinomatous and sarcomatous components had a mild heterogeneity; the two components may evolve from common ancestral cells. High PD-L1 expression suggests that immunotherapy could be used as a potential therapy for PSC patients, while patients with negative immune-responsive genes need to be screened out. Altogether, these findings further highlight that the detection of genetic alteration and PD-L1 expression plays an important role in treatment of patients with PSC.
