Comparative Study of FISH and Immunohistochemistry Assays for the Detection of ALK-Positive Non-Small-Cell Lung Cancers: Report of a Series of 878 Cases
Florian Cabillic, Dan Chiforeanu, Frederic Dugay, Romain Corre, Herve Lena, Michele Le Calve, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau. CHU Pontchaillou, Rennes, France; Faculty of Medicine, Rennes, France
Background: Crizotinib is indicated for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). These tumors can be identified by the FDA-approved-ALK companion diagnostic fluorescent in situ hybridization (FISH) assay. However, the place of immunohistochemistry (IHC) testing still debates. We studied the performances of these 2 techniques in a series of 878 NSCLC.
Design: The cohort consisted of 608 male and 270 female patients with a NSCLC: 709 adenocarcinomas (ADC), 115 squamous cell carcinomas (SSC), 24 large cell carcinomas (LCC), 2 adenosquamous cell carcinomas (ADSC), 1 large cell neuroendocrine carcinoma and 27 unclassifiable cases (UC). Formol-fixed paraffin-embedded tissue sections were prospectively analyzed between June 2011 and April 2012 by FISH (Abbott-Vysis ALK Break Apart FISH Probe) and IHC (Anti-ALK antibody (ab17127)5A4 clone, Abcam and Roche-Ventana BenchMark XT system).
Results: FISH analyses were non contributive in 209/878 (23%). Among them, 201 were IHC-negative (neg) and 8 IHC-positive (pos). IHC analyses were non contributive in 11/878 (1%) of the cases which were all FISH-neg. A total of 658 cases were successfully analyzed both by FISH and IHC: 17 were FISH-pos/IHC-pos, 8 FISH-pos/IHC-neg, 7 FISH-neg/IHC-pos and 626 FISH-neg/IHC-neg. The overall concordance between the 2 techniques was 98%. An ALK-positivity was detected by FISH and/or IHC in 40/878 (4.6%) of the cases (37 ADC, 1SSC, 1ASC and 1 UC). Among them, 8/40 (20%) couldn't be classified as ALK-positive NSCLC because IHC-pos (3 low and 5 strong immunostaining) / FISH-non contributive results; 5/40 (13%) with a IHC-pos (low immunostaining) / FISH-neg results were classified as ALK-neg NSCLC and 8/40 (20%) FISH-pos / IHC-neg cases were classified as ALK-pos NSCLC. Interestingly, 2 cases showed a strong immunoreactivity by IHC but a FISH-neg result confirmed with several different FISH probes. Finally, only 17/40 cases (43%) were FISH and IHC-pos.
Conclusions: Our data highlight some discrepancies between ALK testing by FISH and IHC inciting to routinely perform these 2 assays in front to enhance the detection rate of the ALK-positive NSCLC.
Monday, March 4, 2013 1:00 PM
Poster Session II # 281, Monday Afternoon