Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing
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 s...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 May 2013
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| In: |
Lung cancer
Year: 2013, Volume: 81, Issue: 2, Pages: 200-206 |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2013.04.015 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.lungcan.2013.04.015 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0169500213001657 
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| Author Notes: | Maximilian v. Laffert, Arne Warth, Roland Penzel, Peter Schirmacher, Danny Jonigk, Hans Kreipe, Hans-Ulrich Schildhaus, Sabine Merkelbach-Bruse, Reinhard Büttner, Simone Reu, Rosi Kerler, Andreas Jung, Thomas Kirchner, Cornelius Wölfel, Iver Petersen, Regulo Rodriguez, Wolfram Jochum, Holger Bartsch, Annette Fisseler-Eckhoff, Erika Berg, Dido Lenze, Manfred Dietel, Michael Hummel |
| Summary: | 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. |
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| Item Description: | Gesehen am 21.09.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2013.04.015 |