1208 - Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of the first intern round robin panel testing (8...
|Date||28 September 2012|
|Event||ESMO Congress 2012|
Non-Small-Cell Lung Cancer, Metastatic
|Presenter||Maximilian von Laffert|
M. von Laffert1, P. Schirmacher2, H. Kreipe3, R. Büttner4, I. Petersen5, W. Jochum6, M. Dietel7, M. Hummel8
The reliable identification of NSCLC patients with breaks in the gene of the anaplastic lymphoma kinase (ALK) is crucial for the induction of therapy with inhibitors (e.g. Crizotinib) against the ALK activity. The implementation of round robin tests is essential to certificate institutes of pathology which are capable to perform ALK-testing with high reliability.Material and methods
Tissue microarrays consisting of 10 NSCLC cases (all adenocarcinomas; 3 cores for each case) were independently tested for ALK-expression by immunohistochemistry (IHC) and genomic ALK-breaks by FISH in 8 institutes of pathology (listed authors on behalf of the group: Universities of Berlin, Heidelberg, Hannover, Köln, München, Jena, St. Gallen and Wiesbaden). 5 cases were ALK-break positive (one case with a low percentage of ALK-break positive cells; 20%) whereas the remaining 5 cases were clearly ALK-break negative as determined by blinded testing independently performed in Berlin and Heidelberg. RT-PCR was carried out to confirm the presence of an EML4-ALK fusion in the ALK-break positive cases.Results
All 8 participants identified the 5 ALK-break negative cases correctly (IHC and FISH) and 4 of the FISH-positive cases were detected by all but one of the participants (FISH). The remaining ALK-break positive case with a low number of affected tumour cells was scored negative by 3 of the 8 participants. IHC for the detection of ALK-expression revealed heterogeneous results in the ALK-break positive cases whereas ALK-break negative cases were consistently scored negative by all participants.Conclusion
Our round robin test for ALK-testing demonstrates that unequivocal ALK-break negative NSCLC cases were consistently scored negative by all participants by means of FISH and IHC. In contrast ALK-IHC (ALK-expression) with currently available antibodies clearly failed to detect all ALK-translocation positive lung cancers. Thus, application and validation of more reliable ALK-antibodies is required before IHC screening can be recommended. ALK-break positivity appears to be reliably detectable (FISH) in cases with a high percentage of affected tumour cells. Cases with low numbers of ALK-break positive tumour cells (between 15% and 20%) remain a diagnostic challenge.Disclosure
All authors have declared no conflicts of interest.