Pathology Outlines

Stains & molecular markers
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]

Page views in 2019: 7,692

Page views in 2020 to date: 5,945

Table of Contents

Cite this page: Pernick N. ALK. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsalk.html. Accessed August 11th, 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