Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Genomic Landscape of Pulmonary Sarcomatoid Carcinoma: Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung; Cancer Res Treat. 2024;56(2):442-454. Published online November 14, 2023; DOI: https://doi.org/10.4143/crt.2023.764

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Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

Citations

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A Phase II Study of Durvalumab, Doxorubicin, and Ifosfamide in Recurrent and/or Metastatic Pulmonary Sarcomatoid Carcinoma (KCSG LU-19-24)
Miso Kim, Jeonghwan Youk, Tae Min Kim, Gyeong-Won Lee, Dong-Wan Kim, Bhumsuk Keam
Clinical Lung Cancer.2026; 27(3): 58. CrossRef
Genomic characterization of pulmonary sarcomatoid adenocarcinoma: a paired whole-exome sequencing study of carcinomatous and sarcomatous components
Jing Lin, Yuzhong Yang, Mengqing Liu, Fan Yang, Shaofeng Jiang, Longkuan Xu, Xiang Zheng, Hui Wei, Xuyan Wen, Guining Xu, Ruolan Weng, Jinhua Zheng, Shengjun Xiao
Frontiers in Oncology.2026;[Epub] CrossRef
Prevalence of High Programmed Death-Ligand 1 Expression in Pulmonary Sarcomatoid Carcinoma: A Systematic Review and Meta-Analysis
Yusuke Hamakawa, Aya Shiba, Yohei Noguchi, Hiroyuki Shinohara, Yuko Higashi, Masaharu Aga, Kazuhito Miyazaki, Yuri Taniguchi, Yuki Misumi, Yoko Agemi, Tsuneo Shimokawa, Hiroaki Okamoto, Nobuyuki Horita, Yukiko Nakamura
JTO Clinical and Research Reports.2026; 7(10): 101046. CrossRef
Pulmonary pleomorphic carcinoma associated with cystic airspace and recurrent spontaneous pneumothorax: A case report
Qiangsheng Li, Jing Zhang, Youjie Gong, Xudong Wan, Song Zhang, Zhongwang Li, Jun Liu
Oncology Letters.2025; 30(1): 1. CrossRef
Combination of epirubicin and cyclophosphamide for the treatment of advanced pulmonary sarcomatoid carcinoma: A case report and literature review
Ruoyu Deng, Jialing Lv, Fang Wang, Yanqiong Chen, Junfeng Wang, Lin Wang, Lixia Mu, Zhijun Zhang, Wen Zhang, Chao Zhang
Journal of Cancer Research and Therapeutics.2025; 21(2): 512. CrossRef
Challenges in the Recognition and Management of Metastatic Sarcomatoid Carcinoma Masquerading As Post-traumatic Hematoma
Abigayle Wyer, Mena Louis, Richard Adams, Raven Richardson, Ezra Ellis, Brian Gibson
Cureus.2025;[Epub] CrossRef
Distinct Clinicogenomic Features and Immunotherapy Associations in Pulmonary Sarcomatoid Carcinoma: A Multicenter Retrospective Study
Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J. Cooper, Joao V. Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Valentina Santo, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L. Gibbons, Ara A. Vaporc
Journal of Thoracic Oncology.2025; 20(12): 1763. CrossRef
Exceptional Response to Immunotherapy-based Treatment in Compound EGFR-Mutated Oligometastatic Pulmonary Sarcomatoid Carcinoma: A Case Report
Ayushi Gianchandani, Darshana Desai, Janani Sambath, Darshana Patil, Prashant Kumar, Shambhavi Singh, Chetan Madre, Ruturaj Deshpande, Anjali Parab, Niyati Shah, Darshit Shah, Pritam Kataria, Shrikanth Atluri, Marzi Mehta, Aditya Shreenivas, Rajan Datar,
Journal of Immunotherapy and Precision Oncology.2025; 8(3): 206. CrossRef
Immune Checkpoint Inhibitor Monotherapy for Patients With Pulmonary Sarcomatoid Carcinoma—The Optimal Therapeutic Strategy for This Rare Lung Cancer Subtype?
Jennifer M. Boland, Ying-Chun Lo, Aaron S. Mansfield
Journal of Thoracic Oncology.2025; 20(12): 1735. CrossRef
PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Ka
American Journal of Surgical Pathology.2024; 48(10): 1233. CrossRef

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Genetic Alterations in Preinvasive Lung Synchronous Lesions: Soyeon Ahn, Jisun Lim, Soo Young Park, Hyojin Kim, Hyun Jung Kwon, Yeon Bi Han, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung; Cancer Res Treat. 2020;52(4):1120-1134. Published online June 5, 2020; DOI: https://doi.org/10.4143/crt.2020.307

Abstract PDF Supplementary Material PubReader ePub

Purpose
Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD)
Materials and Methods
We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing.
Results
Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions.
Conclusion
Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

Citations

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Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma
Jisun Lim, Yeon Bi Han, Soo Young Park, Soyeon Ahn, Hyojin Kim, Hyun Jung Kwon, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung
Cells.2021; 10(12): 3484. CrossRef

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