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Stains

mTOR


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 20 May 2012, last major update May 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

Definition
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● Mammalian Target Of Rapamycin; also known as mechanistic target of rapamycin, FK506 binding protein 12-rapamycin associated protein 1/FRAP1 (Wikipedia)
● Member of PI3-kinase related family; protein encoded by FRAP1 gene; serine/threonine protein kinase that regulates cell growth, proliferation, motility and survival; also protein synthesis and transcription

Diagrams
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The mTOR signaling pathway


AKT-mTOR signaling pathway


EGFR mediated pathways that function through mTOR

Clinical features
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● mTOR inhibitors may be useful therapeutics, because mTOR is critical for tumor growth; however treatment with rapamycin or mTOR inhibitors may activate compensatory pathways (J Biol Chem 2012 May 3 [Epub ahead of print]), and single agents have limited effectiveness (Hematol Oncol Clin North Am 2012;26:483)
● First generation mTOR inhibitors are FDA approved for renal cell carcinoma (Expert Opin Ther Targets 2012 Apr 12 [Epub ahead of print], Therapy 2011;8:359)
● Possible treatment for hormone receptor+ breast cancer (Ann Oncol 2012 May 2 [Epub ahead of print])

Uses by pathologists
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● None at this time

Micro images
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Breast carcinoma staining for mTOR protein is variable: (A) negative; (B) weak cytoplasmic; (C) moderate cytoplasmic; (D) strong cytoplasmic expression (D)


Normal breast tissue staining is variable: (A) negative mTOR protein expression; (B) weak cytoplasmic expression; (C) moderate cytoplasmic expression; (D) strong staining in breast cancer tissue for comparison


Inhibition of AKT/mTOR and ERK MAPK


Chordoma


Malignant peripheral nerve sheath tumor


Synovial sarcoma, rhabdomyosarcoma and schwannoma

Positive staining - disease
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● Thyroid: papillary carcinoma (cytoplasmic and variable nuclear staining, Mod Pathol 2011;24:1553)
● RICTOR, a major component of the mTOR complex 2, is significantly overexpressed in well-differentiated leiomyosarcoma (Mod Pathol 2012;25:197)

End of Stains > mTOR

Ref Updated: 5/7/12


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