Field of interest
Breast carcinogenesis and progression.
Focus
1 Hypoxia
Tumour hypoxia is one of the hallmarks of solid tumours. Hypoxia is a powerful trigger of angiogenesis and associated with carcinogenesis, tumour progression and resistance to therapy. Cellular hypoxia triggers a broad response that is primarily mediated by the heterodimeric transcription factor hypoxia inducible factor alpha (HIF-1a). Several studies have associated HIF-1 overexpression with human cancer progression. HIF-1 is often overexpressed in colon, breast, gastric, lung, skin, ovarian, pancreatic, prostate and renal carcinomas, and is associated with cell proliferation (Zhong et al., 1999). Immunohistochemical analyses have shown that increased levels of intracellular HIF-1 are associated with breast carcinogenesis (Bos et al., 2001) and poor prognosis in invasive breast cancer (Bos et al.2002). Our fundamental hypoxia research line focuses on novel genes that regulate HIF-1alpha, as well as novel downstream targets of HIF-1alpha. The translational research lines address the clinical relevance of hypoxia associated phenomena in breast carcinogenesis and progression. Further, we develop antibodies to hypoxia related proteins for molecular imaging and therapeutics.
2 Hereditary breast cancer
We study carcinogenesis and classification of hereditary breast tumors. We have described overexpression of EGFR as a hallmark of hereditary breast cancer, developed a clinically applicable classifier for hereditary vs sporadic breast cancer, and have found clues for inactivation of FANCD2 in hereditary breast carcinogenesis.
3 Breast cancer prevention through genetic monitoring of nipple fluid
Studies are ongoing to establish genetic monitoring (especially methylation analysis) of nipple fluid as a means to do early detection of breast premalignancies to prevent breast cancer in high risk patients. We have shown that intranasal oxytocin is crucial for successful nipple aspiration. Further, methylation appeared to occur in both sporadic and hereditary cancer.
4 Sentinel node
We evaluate several issues related to the implementation of the Sentinel Node procedure in breast cancer. We try to predict second echelon positivity in sentinel node positive patients, and study mechanical displacement of breast cells to the sentinel node.
5 HER2 testing
We work on optimizing of HER2 testing by comparing in situ techniques with a novel PCR technique (Multiplex Ligation-dependent Probe Amplification). The latter technique shows promising results.