Stains & CD markers
PTEN
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: PTEN [title]
PTEN
Last author update: 1 July 2016
Last staff update: 18 June 2021
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: PTEN [title]
Table of Contents
Definition / general | Terminology | Diagrams / tables | Clinical features | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Molecular / cytogenetics descriptionCite this page: Enwere E, Chan A. PTEN. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainspten.html. Accessed October 2nd, 2023.
Definition / general
- Phosphatase and tensin homologue deleted on chromosome TEN (at 10q23)
- PTEN gene encodes a 403 amino acid cytosolic lipid phosphatase that negatively regulates AKT activity by dephosphorylating phosphatidylinositol 3,4,5-trisphosphate (PIP3)
- There is a secreted form of PTEN referred to as PTEN-Long or PTEN-L; PTEN-L includes an extra 173 amino acids at the N terminal of PTEN; PTEN-L secreted from one cell can exhibit phosphatase activity in neighboring cells (Science 2013;341:399)
- PTENĪ± is an isoform of PTEN that also contains a 173 amino acid N terminal extension; it is localized to the mitochondria (Cell Metab 2014;19:836)
- Tumor suppressor gene that is commonly lost in human cancer
- Has important role in cell cycle regulation and apoptosis
- Heavily regulated by post-translational modifications, including:
- Oxidation or nitrosylation (C71, C124, C83)
- Ubiquitination (K13 and K289)
- SUMOlyation (K254, K266)
- Acetylation (K125, K128, K163, K402)
Terminology
- Also called Mutated in Multiple Advanced Cancers 1 (MMAC1)
Diagrams / tables
Images hosted on other servers:
Drug targets within the PI3K signalling network
Effects
Activating pathways
Clinical features
- PTEN hamartoma tumor syndrome (PHTS) is a spectrum of human pathologies that result from mutations in PTEN (Am J Surg Pathol 2012;36:671); they include Cowden syndrome, Bannayan-Riley-Rubvalcaba syndrome, Proteus syndrome and Proteus-like syndrome
- Inherited PTEN mutations are also associated with:
- Lhermitte Duclos syndrome (cerebellum dysplastic hamartoma, Ann Neurol 1991;29:517)
- Juvenile polyposis of infancy (Nat Genet 1998;18:12)
- Segmental overgrowth (Eur J Hum Genet 2007;15:767)
- Autism with macrocephaly (J Med Genet 2005;42:318)
- Mutations are associated with resistance to anti-androgen therapy
- Also Cowden syndrome, carcinomas of bladder, breast, endometrium (Mod Pathol 2012;25:1508), esophagus (Hum Pathol 2013;44:829), head and neck (squamous cell carcinoma), kidney (Am J Surg Pathol 2011;35:1549), lung, prostate (Mod Pathol 2013;26:835), stomach and thyroid; glioblastoma, melanoma
- Reduced PTEN expression predicts relapse in breast carcinoma patients treated with tamoxifen (Mod Pathol 2005;18:250)
- Gross rearrangements of PTEN locus occur in prostate cancer and can be detected by a 'break-apart' FISH assay (Mod Pathol 2012;25:902)
- No specific targeted therapy against PTEN currently exist; other inhibitors targeting the PI3K / AKT / mTOR pathway may provide some benefit for patients
Uses by pathologists
- Loss of nuclear PTEN expression in adenomatous thyroid nodules is sensitive and specific for Cowden syndrome (Am J Surg Pathol 2011;35:1505)
- Loss of cytoplasmic PTEN may distinguish intraductal prostatic carcinoma from high grade PIN (Mod Pathol 2013;26:587)
- Immunohistochemistry and FISH can detect deletion or decreased expression of PTEN
Microscopic (histologic) images
Images hosted on other servers:
Colon, carcinoma & adenoma
Kidney
Uterus, endometrial carcinoma
Positive staining - normal
- Found in almost all body tissue
Positive staining - disease
- Various carcinomas
Negative staining
- Frequent loss of expression in carcinoma
Molecular / cytogenetics description
- PCR and next generation sequencing have been used to detect specific PTEN mutations, however, many different mutations have been described (Am J Pathol 2000;157:1123)
- Many different types of PTEN mutations have been described (deletions, frameshift, missense, nonsense, etc.)
- Loss of PTEN activity causes an upregulation in the AKT pathway
- Exon 5, the area that encodes for the phosphatase activity, appears to be a hotspot for mutations (Cell Mol Life Sci 2012;69:1475)
- PTEN mutations have been associated with several syndromes including Cowden, Bannayan-Riley-Ruvalcaba, Lhermitte-Duclos and Proteus-like (J Med Genet 2004;41:323)
- Approximately 10% of benign melanocytic nevi demonstrate some PTEN loss (J Am Acad Dermatol 2003;49:865)
- Between 10 and 30% of melanomas harbor a PTEN aberration (Cell Mol Life Sci 2012;69:1475)
- PTEN and NRAS appear to be mostly mutually exclusive (Cancer Res 2000;60:1800)
- PTEN loss has been shown to confer BRAF resistance in cell lines (Cancer Res 2011;71:2750)
