Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples: Chang Gok Woo, Seung-Myoung Son, Ho-Chang Lee, Hye Sook Han, Ki Hyeong Lee, Dohun Kim, Eung-Gook Kim, Ok-Jun Lee; Cancer Res Treat. 2022;54(3):737-743. Published online September 24, 2021; DOI: https://doi.org/10.4143/crt.2021.773

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Purpose
Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.
Materials and Methods
We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.
Results
Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.
Conclusion
The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Citations

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Shuo Li, Wenyuan Li, Bin Liu, Kostyantyn Krysan, Steven M. Dubinett
Cancer Research Communications.2024; 4(7): 1738. CrossRef
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Alessandro Bonis, Andrea Dell’Amore, Vincenzo Verzeletti, Luca Melan, Giovanni Zambello, Chiara Nardocci, Giovanni Maria Comacchio, Federica Pezzuto, Fiorella Calabrese, Federico Rea
Journal of Clinical Medicine.2023; 12(4): 1411. CrossRef
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Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
Thoracic Cancer.2023; 14(26): 2635. CrossRef
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Sharia Hernandez, Rossana Lazcano, Alejandra Serrano, Steven Powell, Larissa Kostousov, Jay Mehta, Khaja Khan, Wei Lu, Luisa M. Solis
Frontiers in Oncology.2022;[Epub] CrossRef

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EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors: Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han; Cancer Res Treat. 2018;50(3):908-916. Published online September 19, 2017; DOI: https://doi.org/10.4143/crt.2017.378

Abstract PDF PubReader ePub

Purpose
Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy.
Materials and Methods
Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively.
Results
EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026).
Conclusion
EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.

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10,200 View
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34 Web of Science
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