PMID- 25898958
OWN - NLM
STAT- MEDLINE
DCOM- 20160321
LR  - 20200317
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 10
IP  - 5
DP  - 2015 May
TI  - Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell 
      lung carcinomas: a comparative study between small biopsy and excision samples.
PG  - 800-805
LID - S1556-0864(15)32392-3 [pii]
LID - 10.1097/JTO.0000000000000507 [doi]
AB  - INTRODUCTION: The standard diagnostic method for echinoderm 
      microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine 
      kinase translocation is fluorescence in situ hybridization (FISH). Recently, 
      immunohistochemistry (IHC) has been reported as a potential method in screening 
      for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinomas 
      (NSCLC), whereas several authors have reported a discordance between FISH and IHC 
      results. We investigated the heterogeneity of ALK gene rearrangement in excision 
      specimens by FISH and also examined whether the FISH score of ALK gene 
      rearrangement corresponded in excision and biopsy samples from the same patient. 
      METHODS: Twenty ALK IHC-positive patients including six patients treated with 
      crizotinib therapy were evaluated for the presence of ALK FISH. For evaluation of 
      heterogeneity of ALK gene rearrangement in excision specimens, we defined six to 
      10 observation areas in each case, and the number of ALK FISH positive 
      observation areas (>/=15% rearrangement detected) was investigated. ALK FISH score 
      in small biopsy samples was classified as positive (>/=15% rearrangement detected), 
      equivocal (5-14% rearrangement detected), or negative (<4% rearrangement 
      detected). RESULTS: Of a total of 64 tumor observation areas from nine excision 
      specimens, 50 areas were positive for ALK gene rearrangement (81.8%). In the 
      comparison of excision and small biopsy samples, all excision specimens were ALK 
      FISH-positive (100%; 6 of 6), whereas only three of the small biopsy samples in 
      these patients were positive (50%; 3 of 6), two were equivocal (33%; 2 of 6), and 
      one was negative (17%; 1 of 6). The two equivocal patients received crizotinib 
      and showed a response. CONCLUSION: ALK gene rearrangement heterogeneity was 
      observed in NSCLC specimens by FISH. Our findings suggested that 
      IHC-positive/FISH-equivocal cases should not be considered true "false-negatives" 
      when a small biopsy sample was used for ALK analysis.
FAU - Abe, Hideyuki
AU  - Abe H
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan. 
      Electronic address: abe_hideyuki@kurume-u.ac.jp.
FAU - Kawahara, Akihiko
AU  - Kawahara A
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
FAU - Azuma, Koichi
AU  - Azuma K
AD  - Division of Respirology, Neurology, and Rheumatology, Department of Internal 
      Medicine, Kurume University School of Medicine, Kurume, Japan.
FAU - Taira, Tomoki
AU  - Taira T
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
FAU - Takase, Yorihiko
AU  - Takase Y
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
FAU - Fukumitsu, Chihiro
AU  - Fukumitsu C
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
FAU - Murata, Kazuya
AU  - Murata K
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
FAU - Yamaguchi, Tomohiko
AU  - Yamaguchi T
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
FAU - Akiba, Jun
AU  - Akiba J
AD  - Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
FAU - Ishii, Hidenobu
AU  - Ishii H
AD  - Division of Respirology, Neurology, and Rheumatology, Department of Internal 
      Medicine, Kurume University School of Medicine, Kurume, Japan.
FAU - Okamoto, Isamu
AU  - Okamoto I
AD  - Center for Clinical and Translational Research, Kyushu University Hospital, 
      Fukuoka, Japan.
FAU - Hoshino, Tomoaki
AU  - Hoshino T
AD  - Division of Respirology, Neurology, and Rheumatology, Department of Internal 
      Medicine, Kurume University School of Medicine, Kurume, Japan.
FAU - Takamori, Shinzou
AU  - Takamori S
AD  - Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
FAU - Kage, Masayoshi
AU  - Kage M
AD  - Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anaplastic Lymphoma Kinase
MH  - Biopsy
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/*pathology/surgery
MH  - False Negative Reactions
MH  - Female
MH  - *Gene Rearrangement
MH  - Genetic Heterogeneity
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung/*pathology
MH  - Lung Neoplasms/*genetics/*pathology/surgery
MH  - Male
MH  - Middle Aged
MH  - Receptor Protein-Tyrosine Kinases/analysis/*genetics
EDAT- 2015/04/23 06:00
MHDA- 2016/03/22 06:00
CRDT- 2015/04/23 06:00
PHST- 2015/04/23 06:00 [entrez]
PHST- 2015/04/23 06:00 [pubmed]
PHST- 2016/03/22 06:00 [medline]
AID - S1556-0864(15)32392-3 [pii]
AID - 10.1097/JTO.0000000000000507 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2015 May;10(5):800-805. doi: 10.1097/JTO.0000000000000507.