Stains
WWTR1

Authors: Angela Chan, MSc. (see Authors page)
Editor: Emeka Enwere, M.D.

Revised: 27 April 2017, last major update April 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: WWTR1
Cite this page: WWTR1. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainswwtr1.html. Accessed October 23rd, 2017.
Definition / general
  • WWTR1, also known as TAZ (Transcriptional coactivator with PDZ binding motif), is a transcriptional coactivator that regulates expression of genes involved in cell proliferation and differentiation
  • The human WWTR1 gene codes for a protein with an apparent molecular weight of 50 - 55 kDa
Essential features
  • WWTR1 is negatively regulated by the Hippo signal transduction pathway
    • This pathway controls organ size by dynamically balancing the processes of cell proliferation and apoptosis (Nat Rev Cancer 2015;15:73)
  • WWTR1 functions interchangeably with its paralog, Yes associated protein (YAP)
  • In the absence of Hippo signaling, WWTR1 is predominantly present in the nucleus, where it interacts with various transcription factors to regulate gene expression
  • In the presence of Hippo signaling, it is retained in the cytoplasm and degraded
  • WWTR1 is overexpressed in many types of cancer (Cancer Cell 2016;29:783) and promotes metastasis through epithelial mesenchymal transition (Genes Dev 2012;26:54)
  • The human WWTR1 gene is on chromosome 3q24
Terminology
  • WWTR1 (WW Domain Containing Transcription Regulator 1)
  • TAZ
Sites
  • Ubiquitously expressed predominantly in the nucleus but cytoplasmic expression is likely in cells with active Hippo pathways
Pathophysiology
Clinical features
Case reports
Treatment
  • TAZ does not bind to DNA on its own but through interaction with TEAD transcription factors
  • Interruption of the TAZ-TEAD interaction can potentially be useful in the inhibition of the oncogenic role of TAZ
  • Currently no therapeutic is available to interrupt TAZ-TEAD interaction
  • Verteporfin is shown to block YAP-induced tumorigenesis (Genes Dev 2012;26:1300)
Microscopic (histologic) images

Images hosted on other servers:
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TAZ / YAP associated with increased grade

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Staining of WWTR1 in osteosarcoma

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YAP / TAZ widely expressed and
activated across multiple
histological sarcoma types
Positive stains
  • Various types of cancer: brain, colon, kidney, liver, lung, pancreas
Negative stains
  • Skin, soft tissue
Board review question #1
    Which assay(s) would support a diagnosis of epithelioid hemangioendothelioma with WWTR1-CAMTA1 fusion?

  1. CAMTA1 immunohistochemistry
  2. WWTR1-CAMTA1 break apart FISH
  3. WWTR1 immunohistochemistry
  4. (a) or (b)
  5. (b) or (c)
Board review answer #1
D. While break apart FISH is sufficient for molecular confirmation, CAMTA1 mis-expression in epithelioid hemangioendotheliomas may also be indicative of this translocation event.