Stains & molecular markers
ALK
Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.
PubMed Search: ALK[title], ALK1[title]
ALK
Author: Nat Pernick, M.D.
Topic Completed: 1 January 2014
Minor changes: 30 December 2019
Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.
PubMed Search: ALK[title], ALK1[title]
Table of Contents
Definition / general | Pathophysiology | Diagrams / tables | Clinical features | Methods | Microscopic (histologic) images | Positive staining - normal | Positive staining - tumors | Negative staining | Molecular / cytogenetics imagesCite this page: Pernick N. ALK. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsalk.html. Accessed May 24th, 2020.
Definition / general
- See also NPM-ALK fusion protein
- Anaplastic lymphoma kinase gene is at 2p23; protein is called ALK1, CD246
- Membrane spanning tyrosine kinase receptor, member of insulin receptor family
- Is NOT the same as Ki-1/CD30, contrary to some references
- Interpretation: usually cytoplasmic and nuclear staining
- References: OMIM #105590
Pathophysiology
- Ligand is growth factor pleiotrophin
- 3' end contains catalytic domain of tyrosine kinase
- Has important role in brain development
- Part of ~ 20 translocations associated with large B-cell lymphoma (Int J Clin Exp Pathol 2009;2:508, Adv Hematol 2012;2012:529572), nonsmall cell lung carcinoma (Mol Cancer 2010;9:188), inflammatory myofibroblastic tumor (J Signal Transduct 2012;2012:123253)
Diagrams / tables
Images hosted on other servers:
ALK signaling
Pathways in ALK+ anaplastic large cell lymphoma
Clinical features
- First discovered associated with anaplastic large cell lymphoma in 1994 (Science 1994;263:1281)
- t(2;5) is associated with T cell anaplastic lymphoma via fusion of ALK and NPM (nucleophosmin protein), but also variants (Genes Chromosomes Cancer 2002;34:354)
- ALK+ primary anaplastic large cell lymphomas have favorable prognostic significance (Blood 1999;93:3913), including primary CNS ALCL (Am J Surg Pathol 2003;27:487); also favorable in inflammatory myofibroblastic tumors (Am J Surg Pathol 2007;31:509)
- ALK- cases of primary anaplastic large cell lymphoma are associated with trisomy 2 (Mod Pathol 2005;18:235); consensus criteria for diagnosis are lacking (Am J Clin Pathol 2007;127:707)
- ALK mutation may cause hereditary hemorrhagic telangiectasia type 2 (J Dent Res 2006;85:705)
Methods
- Prognostic value in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor (see above)
- Predictive marker for therapy in nonsmall cell lung cancer (Mod Pathol 2013;26:1468, Mod Pathol 2013;26:1545, Arch Pathol Lab Med 2012;136:1201)
- Differentiate inflammatory myofibroblastic tumor (ALK+) from ALK negative spindled neoplasms in:
- Bladder (Mod Pathol 2007;20:592, Urol Ann 2012;4:115)
- Female genital tract (Arch Pathol Lab Med 2012;136:623)
- Soft tissue (Am J Surg Pathol 2001;25:1364)
Microscopic (histologic) images
Images hosted on other servers:
Anaplastic lymphoma
Anaplastic lymphoma: various images
Diffuse large B cell lymphoma (fig B)
Inflammatory myofibroblastic tumor (IMT) of bladder
IMT of abdomen
IMT of larynx
(fig 2C)
IMT-pelvis
Inflammatory breast carcinoma is ALK-
Neuroblastoma
Renal cell carcinoma with ALK gene rearrangement
Positive staining - normal
- Embryonic neurons of central and peripheral nervous systems, weakly positive in adult brain
- Normal small intestine, T cells
- Weakly positive in colon, prostate
Positive staining - tumors
- T/null cell anaplastic lymphomas (most), inflammatory myofibroblastic tumor (variable, Am J Surg Pathol 2001;25:1364, Am J Surg Pathol 2001;25:761)
- Diffuse large B cell lymphoma (rarely, Mod Pathol 2007;20:310)
- Low level expression in some rhabdomyosarcomas, lipogenic tumors, Ewing / PNET, MFH, leiomyosarcoma and other soft tissue tumors (Hum Pathol 2004;35:711)
- Rarely renal cell carcinoma (Mod Pathol 2012;25:1516, Korean J Pathol 2013;47:52)
Negative staining
- Fibromatosis, GIST, nodular fasciitis and normal lymphoid tissue
Molecular / cytogenetics images
Images hosted on PathOut server:
Images kindly provided by LeicaBiosystems Amsterdam:
ALK / EML4 t(2;2); inv(2)
ALK (2p23)
Images hosted on other servers:
FISH: ALK+ large cell lymphoma
