Popat, S., Gonzalez, D., Min, T., Swansbury, J., Dainton, M., Croud, J. G., Rice, A. J., Nicholson, A. G. (2012) ALK translocation is associated with ALK immunoreactivity and extensive signet-ring morphology in primary lung adenocarcinoma. LUNG CANCER, 75 (3). pp. 300-305. ISSN 0169-5002

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Abstract

Background: ALK rearrangement is particularly observed in signet-ring sub-type adenocarcinoma. Since fluorescence in situ hybridization (FISH) is not suitable for mass screening, we aimed to characterize the predictive utility of tumour morphology and ALK immunoreactivity to identify ALK rearrangement, in a primary lung adenocarcinoma dataset enriched for signet-ring morphology, compared with that of other morphology. Methods: 7 adenocarcinomas from diagnostic archives reported with signet-ring morphology were assessed and compared with 11 adenocarcinomas without signet-ring features over the same time period. Growth patterns were reviewed, ALK expression was assessed by standard immunohistochemistry using ALK1 clone and Envision detection (Dako), and ALK rearrangement was assessed by FISH (Abbott Molecular). Associations between groups and predictive utility of tumour morphology and ALK expression using FISH as gold standard were calculated. Results: 2 excision lung biopsy cases with pure (100%) signet-ring morphology and solid patterns demonstrated diffuse moderate cytoplasmic ALK immunoreactivity (2+) and harboured ALK rearrangements (p = 0.007), unlike 5 mixed-signet-ring and 11 non-signet-ring adenocarcinomas, which showed negative or 1+ immunoreactivity; and did not harbour ALK rearrangements (p > 0.1). ALK expression was not associated with ALK copy number. 6 of 7 cases with signet ring morphology stained for TTF-1. Pure signet-ring morphology and moderate ALK expression were both associated with ALK rearranged tumours. Conclusion: ALK rearrangement is strongly associated with ALK immunoreactivity, and was seen only in tumours with pure signet-ring morphology and solid growth pattern. Tumour morphology, growth pattern and ALK immunoreactivity appear to be good indicators of ALK rearrangement, with TTF-1 positivity aiding in proving primary pulmonary origin. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Article
All Authors:	Popat, S., Gonzalez, D., Min, T., Swansbury, J., Dainton, M., Croud, J. G., Rice, A. J., Nicholson, A. G.
Additional Information:	ISI Document Delivery No.: 906BU Times Cited: 0 Cited Reference Count: 20 Popat, Sanjay Gonzalez, David Min, Toon Swansbury, John Dainton, Melissa Croud, James G. Rice, Alexandra J. Nicholson, Andrew G. NHS; Higher Education Funding Council for England We acknowledge NHS funding to the NIHR Biomedical Research Centre. SP is in receipt of a Clinical Senior Lecturer Award from the Higher Education Funding Council for England. Elsevier ireland ltd Clare
Uncontrolled Keywords:	Adenocarcinoma ALK FISH Immunohistochemistry Signet-ring eml4-alk fusion gene cancer egfr expression mutations features
Research teams:	Clinical Units > Other Royal Marsden Services/Clinical Units
Depositing User:	Alexander Smithson
Date Deposited:	01 May 2012 16:18
Last Modified:	01 May 2012 16:18
URI:	http://publications.icr.ac.uk/id/eprint/11510

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