Stains & CD markers

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Last staff update: 18 June 2021

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PubMed Search: PTEN [title]

Angela M.Y. Chan, M.Sc.
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Cite this page: Enwere E, Chan A. PTEN. website. Accessed May 19th, 2024.
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)
  • Also called Mutated in Multiple Advanced Cancers 1 (MMAC1)
Diagrams / tables

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Drug targets within the PI3K signalling network

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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:
  • Mutations are associated with resistance to anti-androgen therapy
  • 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

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Colon, carcinoma & adenoma

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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)
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