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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Stewart, J; James, J; McCluggage, GW; McQuaid, S; Arthur, K; Boyle, D; Mullan, P; McArt, D; Yan, B; Irwin, G; Harkin, DP; Zhengdeng, L; Ong, C-W; Yu, J; Virshup, DM; Salto-Tellez, M

Published Date

  • March 2015

Published In

Volume / Issue

  • 28 / 3

Start / End Page

  • 428 - 436

PubMed ID

  • 25258105

Pubmed Central ID

  • 25258105

Electronic International Standard Serial Number (EISSN)

  • 1530-0285

Digital Object Identifier (DOI)

  • 10.1038/modpathol.2014.114


  • eng

Conference Location

  • United States