Stains & CD markers
ATM

Editor-in-Chief: Debra L. Zynger, M.D.
Joo-Shik Shin, M.B.B.S., Ph.D.

Topic Completed: 29 January 2021

Minor changes: 23 June 2021

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PubMed Search: ATM[TI] stains pathology

Joo-Shik Shin, M.B.B.S., Ph.D.
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Cite this page: Shin JS. ATM. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsatm.html. Accessed October 21st, 2021.
Definition / general
  • Ataxia telangiectasia mutated (ATM), on chromosome 11q22-23, was discovered in 1995 as the single gene, which when mutated causes ataxia telangiectasia (Science 1995;268:1749)
  • Early integral component of the DNA damage response pathway, which is recruited to the site of genetic damage and affects cell cycle arrest (Trends Biochem Sci 2006;31:402)
Essential features
  • Gene mutation responsible for ataxia telangiectasia
  • Integral early component of DNA damage response pathway, without which cells are prone to accumulating mutations and genetic instability
  • Apart from ataxia telangiectasia, also manifests clinically as sensitivity to radiation induced DNA damage and susceptibility to a number of cancers in heterozygote carriers as well as homozygotes
  • Immunostaining for ATM currently restricted to research, though publications have shown relationship to prognosis and treatment response in a number of cancer types
Pathophysiology
  • Loss of function mutations lead to inability to repair DNA damage that accumulates endogenously with metabolic processes, replication errors during cell division or with exposure to exogenous agents (EMBO J 2008;27:589)
  • Subsequent genetic instability, defective reparative response to DNA double strand breaks from ionizing radiation and telomeric shortening with premature cellular senescence contributes to the 2 main clinical manifestations: ataxia telangiectasia and predisposition to cancers (Orphanet J Rare Dis 2016;11:159)
Diagrams / tables

Images hosted on other servers:
ATM in DNA<br>damage response

ATM in DNA
damage response

ATM signaling network

ATM signaling network

Clinical features
  • Ataxia telangiectasia: autosomal recessive inherited condition with cerebellar ataxia, telangiectatic vessels, immunodeficiency, radiation sensitivity and susceptibility to cancers (Orphanet J Rare Dis 2016;11:159)
  • Malignancies typically associated with ataxia telangiectasia include mainly lymphomas and leukemias, especially in childhood and additionally breast, gastric and liver cancers in adulthood (J Clin Oncol 2015;33:202)
  • Increased risk for cancer also seen in ATM mutation carriers, mainly breast and gastrointestinal tract cancers (Clin Genet 2016;90:105)
Interpretation
  • Both nuclear and cytoplasmic staining patterns have been reported
Uses by pathologists
  • No current routine clinical use
Prognostic factors
Microscopic (histologic) images

Contributed by Joo-Shik Shin, M.B.B.S., Ph.D.
Rectal adenocarcinoma

Rectal adenocarcinoma

Positive staining - normal
  • Most normal tissues expected to show some level of staining; for instance, large bowel mucosal epithelium both adjacent to and away from rectal adenocarcinoma (PLoS One 2016;11:e0167675)
Positive staining - disease
Molecular / cytogenetics description
  • Loss of ATM found in genomic analysis of nodal, splenic marginal zone and lymphoplasmacytic lymphomas (Mod Pathol 2012;25:651)
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