Background: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as an effective alternative to fluorescence hybridization in situ (FISH) for the detection of ALK gene rearrangement. However, CB frequently lack adequate cellularity even when the direct smears are cellular. This study aims to assess the utility of ALK immunocytochemical (ICC) staining on direct smears using the cell transfer (CT) technique for the detection of ALK rearrangement. Methods: Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status had been determined by FISH on CB or a concurrent biopsy were identified. ICC staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct smears using the CT technique. ALK immunoreactivity was evaluated using a modified semiquantitative scale. Results were compared with those of FISH. Results: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and FISH was 93.6%. Conclusion: ICC performed on FNA smears using the CT technique is an alternative method for the assessment of ALK rearrangement, especially when CB lack adequate cellularity.

Journal Section:
Editor's choice
Keywords:
Anaplastic lymphoma kinase, Immunocytochemistry, Cell transfer
1.
Kwak EL, Bang YJ, Camidge DR, et al: Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363:1693-1703.
[PubMed]
https://doi.org/10.1056/NEJMoa1006448
2.
Sasaki T, Rodig SJ, Chirieac LR, Janne PA: The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 2010;46:1773-1780.
[PubMed]
https://doi.org/10.1016/j.ejca.2010.04.002
3.
Shaw AT, Kim DW, Nakagawa K, et al: Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385-2394.
[PubMed]
https://doi.org/10.1056/NEJMoa1214886
4.
Camidge DR, Bang YJ, Kwak EL, et al: Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012;13:1011-1019.
[PubMed]
https://doi.org/10.1016/S1470-2045(12)70344-3
5.
Lindeman NI, Cagle PT, Beasley MB, et al: Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med 2013;137:828-860.
[PubMed]
https://doi.org/10.5858/arpa.2012-0720-OA
6.
Weickhardt AJ, Aisner DL, Franklin WA, Varella-Garcia M, Doebele RC, Camidge DR: Diagnostic assays for identification of anaplastic lymphoma kinase-positive non-small cell lung cancer. Cancer 2013;119:1467-1477.
[PubMed]
https://doi.org/10.1002/cncr.27913
7.
Camidge DR, Kono SA, Flacco A, et al: Optimizing the detection of lung cancer patients harboring anaplastic lymphoma kinase (ALK) gene rearrangements potentially suitable for ALK inhibitor treatment. Clin Cancer Res 2010;16:5581-5590.
[PubMed]
https://doi.org/10.1158/1078-0432.CCR-10-0851
8.
Zhou J, Zhao J, Sun K, et al: Accurate and economical detection of ALK positive lung adenocarcinoma with semiquantitative immunohistochemical screening. PLoS One 2014;9:e92828.
[PubMed]
https://doi.org/10.1371/journal.pone.0092828
9.
Paik JH, Choe G, Kim H, et al: Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer: correlation with fluorescence in situ hybridization. J Thorac Oncol 2011;6:466-472.
[PubMed]
https://doi.org/10.1097/JTO.0b013e31820b82e8
10.
Sherman ME, Jimenez-Joseph D, Gangi MD, Rojas-Corona RR: Immunostaining of small cytologic specimens: facilitation with cell transfer. Acta Cytol 1994;38:18-22.
[PubMed]
11.
Gong Y, Joseph T, Sneige N: Validation of commonly used immunostains on cell-transferred cytologic specimens. Cancer 2005;105:158-164.
[PubMed]
https://doi.org/10.1002/cncr.21063
12.
Wu HH, Jones KJ, Cramer HM: Immunocytochemistry performed on the cell-transferred direct smears of the fine-needle aspirates: a comparison study with the corresponding formalin-fixed paraffin-embedded tissue. Am J Clin Pathol 2013;139:754-758.
[PubMed]
https://doi.org/10.1309/AJCP8O7VIGSIXIVS
13.
Ferguson J, Chamberlain P, Cramer HM, Wu HH: ER, PR, and Her2 immunocytochemistry on cell-transferred cytologic smears of primary and metastatic breast carcinomas: a comparison study with formalin-fixed cell blocks and surgical biopsies. Diagn Cytopathol 2013;41:575-581.
[PubMed]
https://doi.org/10.1002/dc.22897
14.
Ilie MI, Bence C, Hofman V, et al: Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK ‘borderline'-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies. Ann Oncol 2015;26:238-244.
[PubMed]
https://doi.org/10.1093/annonc/mdu484
15.
Sun JM, Choi YL, Won JK, et al: A dramatic response to crizotinib in a non-small-cell lung cancer patient with IHC-positive and FISH-negative ALK. J Thorac Oncol 2012;7:e36-e38.
[PubMed]
https://doi.org/10.1097/JTO.0b013e318274694e
16.
Savic S, Bode B, Diebold J, et al: Detection of ALK-positive non-small-cell lung cancers on cytological specimens: high accuracy of immunocytochemistry with the 5A4 clone. J Thorac Oncol 2013;8:1004-1011.
[PubMed]
https://doi.org/10.1097/JTO.0b013e3182936ca9
17.
Tanaka H, Tone K, Hayashi A, et al: Clinical application of immunocytochemical detection of ALK rearrangement on cytology slides for detection or screening of lung adenocarcinoma. Lung Cancer 2013;80:289-292.
[PubMed]
https://doi.org/10.1016/j.lungcan.2013.03.006
© 2015 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2015
You do not currently have access to this content.