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.
Original language | English |
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Pages (from-to) | 428-436 |
Number of pages | 9 |
Journal | Modern Pathology |
Volume | 28 |
Issue number | 3 |
Early online date | 26 Sept 2014 |
DOIs | |
Publication status | Published - 01 Mar 2015 |
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Jacqueline James
- School of Medicine, Dentistry and Biomedical Sciences - Clinical Professor
- Patrick G Johnston Centre for Cancer Research
Person: Academic
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Manuel Salto-Tellez
- School of Medicine, Dentistry and Biomedical Sciences - Clinical Professor
- Patrick G Johnston Centre for Cancer Research
Person: Academic