ALK (Anaplastic Lymphoma Kinase) is a transmembrane molecule that is only normally expressed in some neural tissues.  It has characteristic expression in a significant proportion of Anaplastic Large Cell Lymphoma (ALCL) cases.  It has also been expressed in cases of pleomorphic liposarcoma, inflammatory myofibroblastic tumor, Merkel cell carcinoma, and a small subset of diffuse large B-cell lymphomas.

 

A subset (1-5%) of non-small cell lung carcinomas (usually adenocarcinomas) have an ELM4-ALK mutation, which is often sensitive to the tyrosine kinase inhibitor (TKI) crizotinib (Pfizer).  Newer TKIs, including ceritinib (Novartis) and alectinib (Hoffmann-La Roche), have also been found to be effective.  

 

Historically, ALK translocations have been identified by FISH analysis.  IHC is also an accepted method with an FDA approved test (IHC CDx Assay).  PCR is being studied as an alternative.  ALK antibody clones 5A4 (Novocastra, Leica Biosystems, Buffalo Grove, Illinois), ALK1 (Dako, Santa Clara, California), 1A4 (Origene, Rockville, Maryland) and D5F3 (Cell signaling Technology, Danvers, Massachusetts) have been successfully used to identify ALK mutated lung tumors, with the 5A4 & D5F3 having equivalent sensitivity. 

 

The ALK1 clone is not as sensitive and the 1A4 clone lacks specificity compared to other antibodies.  Please consult the current medical literature for FDA approved tests for ALK translocation identification in non-small cell lung carcinomas.

ALK may stain in a cytoplasmic and/or nuclear pattern.  In ALCL the combined pattern of cytoplasmic and nuclear staining is associated with the t(2;5).

 

In lung ALK staining/expression is cytoplasmic.  Like other markers (e.g. Napsin A), staining may be present in macrophages.  Necrotic tumor, extracellular mucin, and cells of neural origin may also stain.

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