| Literature DB >> 25258105 |
Jonathan Stewart1, Jacqueline James1, Glenn W McCluggage1, Stephen McQuaid1, Kenneth Arthur2, David Boyle1, Paul Mullan3, Darragh McArt4, Benedict Yan5, Gareth Irwin3, D Paul Harkin3, Lei Zhengdeng6, Chee-Wee Ong2, Jia Yu6, David M Virshup6, Manuel Salto-Tellez7.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25258105 DOI： 10.1038/modpathol.2014.114
Source DB: PubMed Journal: Mod Pathol ISSN： 0893-3952 Impact factor: 7.842