Stains & CD markers
ATM
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: ATM[TI] stains pathology
ATM
Author: Joo-Shik Shin, M.B.B.S., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 29 January 2021
Minor changes: 23 June 2021
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: ATM[TI] stains pathology
Table of Contents
Definition / general | Essential features | Pathophysiology | Diagrams / tables | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Molecular / cytogenetics descriptionCite 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
damage response
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
- Factors below are reported in research publications without current routine clinical application
- ATM mutation found in subset of chronic lymphocytic leukemia and may relate to inferior outcome and influence chemotherapy response (Haematologica 2013;98:112)
- May determine susceptibility to blast crisis in chronic myeloid leukemia (DNA Repair (Amst) 2013;12:500)
- May determine radiation resistance in glioma stem cells (Oncol Rep 2013;30:1793)
- ATM mutation suggested as prognostic or predictive marker to immunotherapy response in a number of other tumors, including endometrial cancer, metastatic colorectal cancer, melanoma and bladder cancer (Pathol Res Pract 2020;216:153032, Sci Rep 2019;9:285, PLoS One 2015;10:e0134678, Front Genet 2020;11:933)
- Together with its upstream protein complex MRE11 in the DNA damage response pathway, may be predictive of radiotherapy response and prognosis in rectal cancer (PLoS One 2016;11:e0167675)
Microscopic (histologic) images
Contributed by Joo-Shik Shin, M.B.B.S., Ph.D.
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
- Overexpression seen in prostate cancers compared with normal prostate tissue (Am J Clin Pathol 2004;121:231)
Molecular / cytogenetics description
- Loss of ATM found in genomic analysis of nodal, splenic marginal zone and lymphoplasmacytic lymphomas (Mod Pathol 2012;25:651)
