Pathology Outlines

Stains
WWTR1

Authors: Angela M.Y. Chan, M.Sc., Emeka Enwere, Ph.D.

Topic Completed: 1 April 2017

Minor changes: 28 August 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: WWTR1

Page views in 2019: 51

Page views in 2020 to date: 72

Table of Contents

Cite this page: Chan A, Enwere E. WWTR1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainswwtr1.html. Accessed September 20th, 2020.

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

Deletion of WWTR1 in mice leads to development of renal cysts and emphysema (Proc Natl Acad Sci U S A 2007;104:1631, Am J Physiol Renal Physiol 2008;294:F542) but the overall phenotype is remarkably mild
This may be due to compensation for WWTR1 loss by the YAP paralog

Clinical features

Over 90% of epithelioid hemangioendotheliomas contain a reciprocal t(1;3)(p36;q25) chromosomal translocation (Oncogene 2016;35:929)
This results in the fusion of the N terminal of WWTR1 with the C terminal of CAMTA1, creating a putative oncogene (Sci Transl Med 2011;3:98ra82)
Molecular confirmation of this translocation involves a break apart FISH assay; however, immunohistochemistry performed using an antibody raised against the C terminal of CAMTA1 may serve as a proxy, since CAMTA1 is not otherwise expressed in vascular endothelial tumors (Am J Surg Pathol 2016;40:94, Diagn Pathol 2016;11:75)

Case reports

A rare case of epithelioid hemangioendothelioma as a primary thyroid tumor (Endocr Pathol 2016;27:147)

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:

TAZ / YAP associated with increased grade

Staining of WWTR1 in osteosarcoma

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 style question #1

CAMTA1 immunohistochemistry
WWTR1-CAMTA1 break apart FISH
WWTR1 immunohistochemistry
(a) or (b)
(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.