Anaplastic lymphoma kinase (ALK)-expressing Lung Adenocarcinoma with Combined Neuroendocrine Component or Neuroendocrine Transformation: Implications for Neuroendocrine Transformation and Response to ALK-tyrosine Kinase Inhibitors
| العنوان: | Anaplastic lymphoma kinase (ALK)-expressing Lung Adenocarcinoma with Combined Neuroendocrine Component or Neuroendocrine Transformation: Implications for Neuroendocrine Transformation and Response to ALK-tyrosine Kinase Inhibitors |
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| المؤلفون: | Jiyeon Hyeon, Jongmin Sim, Joungho Han, Yoon-La Choi, Hyunjin Kim |
| المصدر: | Journal of Korean Medical Science |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Lung Neoplasms, Adenocarcinoma, Neuroendocrine differentiation, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Anaplastic lymphoma kinase, Humans, Anaplastic Lymphoma Kinase, Epidermal growth factor receptor, Sulfones, Oncology & Hematology, Histologic Transformation, Protein Kinase Inhibitors, In Situ Hybridization, Fluorescence, Aged, ALK-tyrosine Kinase Inhibitor, Ceritinib, biology, Crizotinib, business.industry, Receptor Protein-Tyrosine Kinases, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, CD56 Antigen, respiratory tract diseases, ErbB Receptors, 030104 developmental biology, Pyrimidines, 030220 oncology & carcinogenesis, Mutation, Cancer research, biology.protein, Female, Original Article, business, Tyrosine kinase, medicine.drug |
| الوصف: | Background Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) are usually effective in lung adenocarcinoma patients with anaplastic lymphoma kinase (ALK) rearrangement. However, even after a good response to ALK-TKI therapy, most patients acquire resistance to these agents. Histological transformation is one of several suggested mechanisms of acquired resistance to ALK-TKIs. The clinicopathologic features of four patients with ALK-expressing adenocarcinoma and neuroendocrine features were analyzed. Methods We selected combined neuroendocrine differentiation in pulmonary adenocarcinoma cases with positive ALK immunostaining. Neuroendocrine differentiation was confirmed by CD56 immunohistochemical stain. Additional ALK fluorescence in situ hybridization (FISH) study and epidermal growth factor receptor (EGFR) mutation tests were also performed. Results All four cases were positive for ALK immunohistochemistry and no EGFR mutations were detected. Interestingly, the results of ALK FISH assays showed rearrangement in only two cases. Three cases showed combined adenocarcinoma and neuroendocrine component without history of ALK-TKI administration; one of them was treated with crizotinib and experienced partial tumor regression. The remaining case had an adenocarcinoma at initial biopsy and she showed a partial response to crizotinib, and neuroendocrine changes were visible on second biopsy. Then she was treated with ceritinib and achieved a partial response. Conclusion We suggest that ALK-rearranged adenocarcinoma with combined neuroendocrine component is responsive to ALK-TKIs. Moreover, even after neuroendocrine transformation as a result of resistance to ALK-TKIs, the tumor may have partial response to second generation ALK-TKIs. Graphical Abstract |
| تدمد: | 1598-6357 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3cca58eb1b53757d579183a849fb43ceTest https://pubmed.ncbi.nlm.nih.gov/29629521Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3cca58eb1b53757d579183a849fb43ce |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15986357 |
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