PMID- 29629521
OWN - NLM
STAT- MEDLINE
DCOM- 20180907
LR  - 20181202
IS  - 1598-6357 (Electronic)
IS  - 1011-8934 (Print)
IS  - 1011-8934 (Linking)
VI  - 33
IP  - 15
DP  - 2018 Apr 9
TI  - 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.
PG  - e123
LID - 10.3346/jkms.2018.33.e123 [doi]
LID - e123
AB  - 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.
CI  - (c) 2018 The Korean Academy of Medical Sciences.
FAU - Sim, Jongmin
AU  - Sim J
AUID- ORCID: 0000-0002-7106-1279
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Korea.
FAU - Kim, Hyunjin
AU  - Kim H
AUID- ORCID: 0000-0001-8336-881X
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Korea.
FAU - Hyeon, Jiyeon
AU  - Hyeon J
AUID- ORCID: 0000-0003-3074-4142
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Korea.
FAU - Choi, Yoon La
AU  - Choi Y
AUID- ORCID: 0000-0002-5788-5140
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Korea.
FAU - Han, Joungho
AU  - Han J
AUID- ORCID: 0000-0003-4424-7008
AD  - Department of Pathology and Translational Genomics, Samsung Medical Center, 
      Sungkyunkwan University School of Medicine, Seoul, Korea. hanjho@skku.edu.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20180409
PL  - Korea (South)
TA  - J Korean Med Sci
JT  - Journal of Korean medical science
JID - 8703518
RN  - 0 (CD56 Antigen)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Sulfones)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - K418KG2GET (ceritinib)
SB  - IM
MH  - Adenocarcinoma/drug therapy/metabolism/*pathology
MH  - Adult
MH  - Aged
MH  - Anaplastic Lymphoma Kinase
MH  - CD56 Antigen/metabolism
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/drug therapy/metabolism/*pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Pyrimidines/therapeutic use
MH  - Receptor Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism
MH  - Sulfones/therapeutic use
PMC - PMC5890087
OTO - NOTNLM
OT  - ALK-tyrosine Kinase Inhibitor
OT  - Adenocarcinoma
OT  - Anaplastic Lymphoma Kinase
OT  - Histologic Transformation
COIS- The authors have no potential conflicts of interest to disclose.
EDAT- 2018/04/10 06:00
MHDA- 2018/09/08 06:00
PMCR- 2018/04/09
CRDT- 2018/04/10 06:00
PHST- 2017/09/05 00:00 [received]
PHST- 2018/01/19 00:00 [accepted]
PHST- 2018/04/10 06:00 [entrez]
PHST- 2018/04/10 06:00 [pubmed]
PHST- 2018/09/08 06:00 [medline]
PHST- 2018/04/09 00:00 [pmc-release]
AID - 33.e123 [pii]
AID - 10.3346/jkms.2018.33.e123 [doi]
PST - epublish
SO  - J Korean Med Sci. 2018 Apr 9;33(15):e123. doi: 10.3346/jkms.2018.33.e123.