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Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2014-09-27)
Jonathan Stewart, Jacqueline James, Glenn W McCluggage, Stephen McQuaid, Kenneth Arthur, David Boyle, Paul Mullan, Darragh McArt, Benedict Yan, Gareth Irwin, D Paul Harkin, Lei Zhengdeng, Chee-Wee Ong, Jia Yu, David M Virshup, Manuel Salto-Tellez
ABSTRACT

The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P=0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tris(tert-butoxy)silanol, 99.999%
Sigma-Aldrich
Anti-GPR177 Antibody, clone YJ5, clone YJ5, from mouse
Sigma-Aldrich
Tris(tert-butoxy)silanol, packaged for use in deposition systems