PMID- 26384434
OWN - NLM
STAT- MEDLINE
DCOM- 20160803
LR  - 20220409
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 90
IP  - 2
DP  - 2015 Nov
TI  - Transformation to large cell neuroendocrine carcinoma as acquired resistance 
      mechanism of EGFR tyrosine kinase inhibitor.
PG  - 364-8
LID - S0169-5002(15)30047-7 [pii]
LID - 10.1016/j.lungcan.2015.09.002 [doi]
AB  - OBJECTIVES: Several different acquired resistance mechanisms to epidermal growth 
      factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy have been 
      described. Although rare, the transformation from adenocarcinoma to small cell 
      carcinoma (SCLC) is one of these important mechanisms. We report a rare case that 
      indicates transformation into large-cell neuroendocrine carcinoma (LCNEC) as an 
      acquired resistance mechanism to EGFR-TKI therapy. MATERIALS AND METHODS: The 
      patient was a 68-year-old male with a diagnosis of cT2N2M0 pulmonary 
      adenocarcinoma with L858R mutation on exon 21. He received lobectomy and 
      underwent several courses of chemotherapies, including EGFR-TKIs, each time he 
      relapsed. He finally relapsed with a mass that protruded into his left main 
      bronchus. Resection of the metastatic site identified LCNEC that retained the 
      original EGFR mutation. Immunohistochemistry revealed the loss of expression of 
      EGFR and retinoblastoma (Rb) in the LCNEC. CONCLUSIONS: This case highlights 
      acquisition of EGFR-TKI resistance by transformation to LCNEC, not SCLC. Loss of 
      EGFR and Rb expression in the LCNEC suggests the same mechanism as transformation 
      to SCLC. Further study is needed to elucidate this mechanism, especially 
      regarding the similarities and differences to SCLC.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Kogo, Mariko
AU  - Kogo M
AD  - Departments of Respiratory Medicine, Kobe City Medical Centre General Hospital, 
      Kobe, Japan. Electronic address: m_k_o_g_o@kcho.jp.
FAU - Shimizu, Ryoko
AU  - Shimizu R
AD  - Departments of Respiratory Medicine, Kobe City Medical Centre General Hospital, 
      Kobe, Japan.
FAU - Uehara, Keiichiro
AU  - Uehara K
AD  - Departments of Pathology, Kobe City Medical Centre General Hospital, Kobe, Japan.
FAU - Takahashi, Yutaka
AU  - Takahashi Y
AD  - Departments of Respiratory Surgery, Kobe City Medical Centre General Hospital, 
      Kobe, Japan.
FAU - Kokubo, Masaki
AU  - Kokubo M
AD  - Departments of Radiation Oncology, Kobe City Medical Centre General Hospital, 
      Kobe, Japan.
FAU - Imai, Yukihiro
AU  - Imai Y
AD  - Departments of Pathology, Kobe City Medical Centre General Hospital, Kobe, Japan.
FAU - Tomii, Keisuke
AU  - Tomii K
AD  - Departments of Respiratory Medicine, Kobe City Medical Centre General Hospital, 
      Kobe, Japan.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150908
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Aged
MH  - Carcinoma, Large Cell/*pathology
MH  - Carcinoma, Neuroendocrine/*drug therapy/*pathology
MH  - Cell Transformation, Neoplastic/*pathology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - ErbB Receptors/*metabolism
MH  - Humans
MH  - Male
MH  - Protein Kinase Inhibitors/*therapeutic use
OTO - NOTNLM
OT  - Acquired resistance
OT  - Epidermal growth factor receptor
OT  - Large-cell neuroendocrine carcinoma
OT  - Transformation
OT  - Tyrosine kinase inhibitor
EDAT- 2015/09/20 06:00
MHDA- 2016/08/04 06:00
CRDT- 2015/09/20 06:00
PHST- 2015/06/25 00:00 [received]
PHST- 2015/08/28 00:00 [revised]
PHST- 2015/09/02 00:00 [accepted]
PHST- 2015/09/20 06:00 [entrez]
PHST- 2015/09/20 06:00 [pubmed]
PHST- 2016/08/04 06:00 [medline]
AID - S0169-5002(15)30047-7 [pii]
AID - 10.1016/j.lungcan.2015.09.002 [doi]
PST - ppublish
SO  - Lung Cancer. 2015 Nov;90(2):364-8. doi: 10.1016/j.lungcan.2015.09.002. Epub 2015 
      Sep 8.