Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples
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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.
Abstract
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.
참고문헌 (18)
- 박세훈, "EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation", Cancer Research and Treatment, 52(4), pp.1288~1290 (2020), 대한암학회[DOI]
- Mok TS, "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma", N Engl J Med, 361, pp.947~957 (2009)
- Norkowski E, "Small-cell carcinoma in the setting of pulmonary adenocarcinoma : new insights in the era of mole-cular pathology", J Thorac Oncol, 8, pp.1265~1271 (2013)
- Sequist LV, "Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors", Sci Transl Med, 3, pp.75~ (2011)[DOI]
- Alam N, "Small-cell carcinoma with an epidermal growth factor receptor mutation in a never-smoker with gefitinib-responsive adenocarcinoma of the lung", Clin Lung Cancer, 11, pp.E1~E4 (2010)
- Niederst MJ, "RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer", Nat Commun, 6, pp.6377~ (2015)
- Lee JK, "Clonal history and genetic rredictors of transformation Into small-cell carcinomas from lung adenocarcinomas", J Clin Oncol, 35, pp.3065~3074 (2017)
- Quintanal-Villalonga A, "Lineage plasticity in cancer : a shared pathway of therapeutic resistance", Nat Rev Clin Oncol, 17, pp.360~371 (2020)
- Offin M, "Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes", J Thorac Oncol, 14, pp.1784~1793 (2019)
- Fukui T, "Epidermal growth factor receptor mutation status and clinicopathological features of combined small cell carcinoma with adenocarcinoma of the lung", Cancer Sci, 98, pp.1714~1719 (2007)
- Levin PA, "Histologic transformation from adenocarcinoma to squamous cell carcinoma as a mechanism of resistance to EGFR inhibition", J Thorac Oncol, 10, pp.e86~e88 (2015)
- Hsieh MS, "Histologic evolution from adenocarcinoma to squamous cell carcinoma after gefitinib treatment", Ann Thorac Surg, 99, pp.316~319 (2015)
- Hsu CL, "Histologic transformation in a patient with lung cancer treated with chemotherapy and pembrolizumab", J Thorac Oncol, 12, pp.e75~e76 (2017)
- Fujita S, "Transformation to SCLC after treatment with the ALK inhibitor alectinib", J Thorac Oncol, 11, pp.e67~e72 (2016)
- Shinohara S, "Squamous cell carcinoma transformation from adenocarcinoma as an acquired resistance after the EGFR TKI therapy in(EGFR-mutated)non-small cell lung cancer", J Thorac Dis, 10, pp.E526~E531 (2018)
- Yao Y, "Histologic transformation from adenocarcinoma to both small cell lung cancer and squamous cell carcinoma after treatment with gefitinib : a case report", Medicine(Baltimore), 97, pp.e0650~ (2018)
- Lu H, "Transformation to small-cell lung cancer following treatment with icotinib in a patient with lung adenocarcinoma", Oncol Lett, 15, pp.5799~5802 (2018)
- Lawson DA, "Tumour heterogeneity and metastasis at single-cell resolution", Nat Cell Biol, 20, pp.1349~1360 (2018)