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Mod Pathol. 2015 Mar;28(3):428-36. doi: 10.1038/modpathol.2014.114. Epub 2014 Sep 26.

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

Author information

1
1] Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, UK [2] Tissue Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
2
Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, UK.
3
Breast & Ovarian Cancer Programmes, Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, Northern Ireland, UK.
4
Tissue Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
5
Cancer Science Institute of Singapore, National University Health System & Yong Loo Lin School of Medicine, NUS, Singapore, Singapore.
6
Cancer and Stem Cell Biology Program, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore, Singapore.
7
1] Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, UK [2] Tissue Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK [3] Cancer Science Institute of Singapore, National University Health System & Yong Loo Lin School of Medicine, NUS, Singapore, Singapore.

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.

PMID:
25258105
DOI:
10.1038/modpathol.2014.114
[Indexed for MEDLINE]
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