PMID- 23669200
OWN - NLM
STAT- MEDLINE
DCOM- 20140501
LR  - 20220330
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 81
IP  - 2
DP  - 2013 Aug
TI  - Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer 
      (NSCLC): results of a multi-centre ALK-testing.
PG  - 200-6
LID - S0169-5002(13)00165-7 [pii]
LID - 10.1016/j.lungcan.2013.04.015 [doi]
AB  - BACKGROUND: The reliable identification of non-small cell lung cancers (NSCLC) 
      with chromosomal breaks in the gene of the anaplastic lymphoma kinase (ALK) is 
      crucial for the induction of therapy with ALK-inhibitors. In order to ensure a 
      reliable detection of ALK-breaks by means of fluorescence in situ hybridization 
      (FISH) testing, round robin tests are essential. In preparation of a nation 
      (German)-wide round robin test we initiated a pre-testing phase involving 8 
      experts in FISH-diagnostics to identify NSCLC cases (n = 10) with a pre-tested 
      ALK-status. In addition, ALK immunohistochemistry (IHC) was performed to assess 
      ALK protein expression. MATERIAL AND METHODS: Sections derived from a tissue 
      microarray, each consisting of 3 cores from 10 NSCLC cases, were independently 
      tested for ALK protein expression by IHC and genomic ALK-breaks by FISH involving 
      8 institutes of pathology. Based on a pre-screening, 5 cases were identified to 
      be clearly ALK-break negative, whereas the remaining 5 cases were ALK-break 
      positive including one case with low percentage (20%) of positive cells. The 
      latter had been additionally tested by RT-PCR. RESULTS: The 5 unequivocal 
      ALK-break negative NSCLC were almost consistently scored negative by means of 
      FISH and IHC by all 8 experts. Interestingly, 4 of the 5 cases with pre-defined 
      ALK-breaks revealed homogenous FISH results whereas IHC for the detection of ALK 
      protein expression showed heterogeneous results. The remaining case (low number 
      of ALK-break positive cells) was scored negative by 3 experts and positive by the 
      other 5. RT-PCR revealed the expression of an EML4-ALK fusion gene variant 1. 
      CONCLUSION: ALK-break negative NSCLC cases revealed concordant homogeneous 
      results by means of FISH and IHC (score 0-1) by all 8 experts. Discordant FISH 
      results were raised in one ALK-break positive case with a low number of affected 
      tumor cells. The remaining 4 ALK-break positive cases revealed concordant FISH 
      data whereas the ALK-IHC revealed very diverse results. The cases with concordant 
      FISH results provide an excellent basis for round robin ALK-FISH testing. As long 
      as standardized ALK-IHC protocols are missing, ALK protein expression cannot by 
      regarded as the method of choice for identification of patients eligible for 
      treatment with ALK inhibitors.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - V Laffert, Maximilian
AU  - V Laffert M
AD  - Institute of Pathology, Campus Charite Mitte, Charite Universitatsmedizin, 
      Chariteplatz 1, 10117 Berlin, Germany. maximilian.von-laffert@charite.de
FAU - Warth, Arne
AU  - Warth A
FAU - Penzel, Roland
AU  - Penzel R
FAU - Schirmacher, Peter
AU  - Schirmacher P
FAU - Jonigk, Danny
AU  - Jonigk D
FAU - Kreipe, Hans
AU  - Kreipe H
FAU - Schildhaus, Hans-Ulrich
AU  - Schildhaus HU
FAU - Merkelbach-Bruse, Sabine
AU  - Merkelbach-Bruse S
FAU - Buttner, Reinhard
AU  - Buttner R
FAU - Reu, Simone
AU  - Reu S
FAU - Kerler, Rosi
AU  - Kerler R
FAU - Jung, Andreas
AU  - Jung A
FAU - Kirchner, Thomas
AU  - Kirchner T
FAU - Wolfel, Cornelius
AU  - Wolfel C
FAU - Petersen, Iver
AU  - Petersen I
FAU - Rodriguez, Regulo
AU  - Rodriguez R
FAU - Jochum, Wolfram
AU  - Jochum W
FAU - Bartsch, Holger
AU  - Bartsch H
FAU - Fisseler-Eckhoff, Annette
AU  - Fisseler-Eckhoff A
FAU - Berg, Erika
AU  - Berg E
FAU - Lenze, Dido
AU  - Lenze D
FAU - Dietel, Manfred
AU  - Dietel M
FAU - Hummel, Michael
AU  - Hummel M
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130510
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
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  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Non-Small-Cell Lung/enzymology/*genetics/pathology
MH  - Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Lung Neoplasms/enzymology/*genetics/pathology
MH  - Receptor Protein-Tyrosine Kinases/*genetics
OTO - NOTNLM
OT  - Anaplastic lymphoma kinase (ALK) gene rearrangement
OT  - Fluorescence in situ hybridization (FISH)
OT  - Immunohistochemistry (IHC)
OT  - Non-small cell lung cancer (NSCLC)
OT  - Round robin test
EDAT- 2013/05/15 06:00
MHDA- 2014/05/03 06:00
CRDT- 2013/05/15 06:00
PHST- 2013/01/25 00:00 [received]
PHST- 2013/04/11 00:00 [revised]
PHST- 2013/04/14 00:00 [accepted]
PHST- 2013/05/15 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2014/05/03 06:00 [medline]
AID - S0169-5002(13)00165-7 [pii]
AID - 10.1016/j.lungcan.2013.04.015 [doi]
PST - ppublish
SO  - Lung Cancer. 2013 Aug;81(2):200-6. doi: 10.1016/j.lungcan.2013.04.015. Epub 2013 
      May 10.