Frontiers in Endocrinology (Dec 2022)
Case report: TP53 and RB1 loss may facilitate the transformation from lung adenocarcinoma to small cell lung cancer by expressing neuroendocrine markers
- Jun Li,
- Jun Li,
- Jun Li,
- Bing Wei,
- Bing Wei,
- Bing Wei,
- Junnan Feng,
- Junnan Feng,
- Junnan Feng,
- Xinxin Wu,
- Xinxin Wu,
- Xinxin Wu,
- Yuxi Chang,
- Yuxi Chang,
- Yuxi Chang,
- Yi Wang,
- Xiuli Yang,
- Haiyan Zhang,
- Sile Han,
- Cuiyun Zhang,
- Cuiyun Zhang,
- Cuiyun Zhang,
- Jiawen Zheng,
- Jiawen Zheng,
- Jiawen Zheng,
- Harry J. M. Groen,
- Anke van den Berg,
- Jie Ma,
- Jie Ma,
- Jie Ma,
- Hongle Li,
- Hongle Li,
- Hongle Li,
- Yongjun Guo,
- Yongjun Guo,
- Yongjun Guo
Affiliations
- Jun Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Jun Li
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Jun Li
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Bing Wei
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Bing Wei
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Bing Wei
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Junnan Feng
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Junnan Feng
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Junnan Feng
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Xinxin Wu
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Xinxin Wu
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Xinxin Wu
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Yuxi Chang
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Yuxi Chang
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Yuxi Chang
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Yi Wang
- Department of Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Xiuli Yang
- Department of Oncology, First Affiliated Hospital of Nanyang Medical College, Nanyang, China
- Haiyan Zhang
- Department of Pathology, First Affiliated Hospital of Nanyang Medical College, Nanyang, China
- Sile Han
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Cuiyun Zhang
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Cuiyun Zhang
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Cuiyun Zhang
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Jiawen Zheng
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Jiawen Zheng
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Jiawen Zheng
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Harry J. M. Groen
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Anke van den Berg
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Jie Ma
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Jie Ma
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Jie Ma
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Hongle Li
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Hongle Li
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Hongle Li
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- Yongjun Guo
- Department of Molecular Pathology, Clinical Pathology Center, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
- Yongjun Guo
- Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
- Yongjun Guo
- Henan International Joint Laboratory of Cancer Molecular Genetics, Zhengzhou, China
- DOI
- https://doi.org/10.3389/fendo.2022.1006480
- Journal volume & issue
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Vol. 13
Abstract
IntroductionTransformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment.Patient and methodWe report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified.ResultsEGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue.ConclusionWe consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy.
Keywords
- small cell lung cancer transformation
- lung adenocarcinoma
- osimertinib
- TP53 and RB1 loss
- MYC amplification
