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Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing.
Lung Cancer 2013; 81(2):200-6LC

Abstract

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.

Authors+Show Affiliations

Institute of Pathology, Campus Charité Mitte, Charité Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany. maximilian.von-laffert@charite.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23669200

Citation

V Laffert, Maximilian, et al. "Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement in Non-small Cell Lung Cancer (NSCLC): Results of a Multi-centre ALK-testing." Lung Cancer (Amsterdam, Netherlands), vol. 81, no. 2, 2013, pp. 200-6.
V Laffert M, Warth A, Penzel R, et al. Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing. Lung Cancer. 2013;81(2):200-6.
V Laffert, M., Warth, A., Penzel, R., Schirmacher, P., Jonigk, D., Kreipe, H., ... Hummel, M. (2013). Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing. Lung Cancer (Amsterdam, Netherlands), 81(2), pp. 200-6. doi:10.1016/j.lungcan.2013.04.015.
V Laffert M, et al. Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement in Non-small Cell Lung Cancer (NSCLC): Results of a Multi-centre ALK-testing. Lung Cancer. 2013;81(2):200-6. PubMed PMID: 23669200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing. AU - V Laffert,Maximilian, AU - Warth,Arne, AU - Penzel,Roland, AU - Schirmacher,Peter, AU - Jonigk,Danny, AU - Kreipe,Hans, AU - Schildhaus,Hans-Ulrich, AU - Merkelbach-Bruse,Sabine, AU - Büttner,Reinhard, AU - Reu,Simone, AU - Kerler,Rosi, AU - Jung,Andreas, AU - Kirchner,Thomas, AU - Wölfel,Cornelius, AU - Petersen,Iver, AU - Rodriguez,Regulo, AU - Jochum,Wolfram, AU - Bartsch,Holger, AU - Fisseler-Eckhoff,Annette, AU - Berg,Erika, AU - Lenze,Dido, AU - Dietel,Manfred, AU - Hummel,Michael, Y1 - 2013/05/10/ PY - 2013/01/25/received PY - 2013/04/11/revised PY - 2013/04/14/accepted PY - 2013/5/15/entrez PY - 2013/5/15/pubmed PY - 2014/5/3/medline KW - Anaplastic lymphoma kinase (ALK) gene rearrangement KW - Fluorescence in situ hybridization (FISH) KW - Immunohistochemistry (IHC) KW - Non-small cell lung cancer (NSCLC) KW - Round robin test SP - 200 EP - 6 JF - Lung cancer (Amsterdam, Netherlands) JO - Lung Cancer VL - 81 IS - 2 N2 - 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. SN - 1872-8332 UR - https://www.unboundmedicine.com/medline/citation/23669200/Anaplastic_lymphoma_kinase__ALK__gene_rearrangement_in_non_small_cell_lung_cancer__NSCLC_:_results_of_a_multi_centre_ALK_testing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-5002(13)00165-7 DB - PRIME DP - Unbound Medicine ER -