| Autor: |
Green AR; Molecular Pathology Research Unit, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, NG5 1PB, UK, andrew.green@nottingham.ac.uk., Barros FF, Abdel-Fatah TM, Moseley P, Nolan CC, Durham AC, Rakha EA, Chan S, Ellis IO |
| Jazyk: |
angličtina |
| Zdroj: |
Breast cancer research and treatment [Breast Cancer Res Treat] 2014 May; Vol. 145 (1), pp. 33-44. Date of Electronic Publication: 2014 Apr 06. |
| DOI: |
10.1007/s10549-014-2925-7 |
| Abstrakt: |
Human epidermal growth factor receptor 2 (HER2) plays an important role in breast cancer progression and provides predictive information for response to targeted therapy including trastuzumab although this is limited. Downstream pathways, such as PI3K/Akt, are associated with HER2/HER3 heterodimerization promoting survival and proliferation amongst cancer cells. Thus, patient outcome and trastuzumab therapy effectiveness might be further characterised by HER2/HER3 dimerisation and its signalling pathways. HER2/HER3 dimerisation status was assessed, using chromogenic in situ Proximity Ligation Assay, in two breast cancer series: early stage primary breast cancer, including 224 HER2+ patients that were not submitted to trastuzumab, and HER2+ breast cancer where patients were treated with adjuvant trastuzumab (n = 143). Levels of biomarkers including PI3K, pAKT, ER, PgR, HER3, BCL2, p53, PTEN and p21 were measured using immunohistochemistry. Levels of HER2/HER3 heterodimers were compared with biomarker expression and patient outcome. An association between high levels of HER2/HER3 dimerisation and absence of hormone receptors, ER and PgR, was observed. We further show for the first time the presence of HER2/HER3 heterodimers and the loss of p21 expression in HER2+ breast cancer predicts a significantly poorer outcome when submitted to adjuvant trastuzumab. Breast cancer patients that reveal high levels of HER2/HER3 dimerisation and loss of p21 are associated with poor survival prognosis in patients with HER2+ breast cancer treated with adjuvant trastuzumab. Further quantification analysis of HER dimer/ligand complexes and downstream signalling pathways will begin to unravel the complex associations with patient outcome and its relationship with sensitivity to targeted treatment. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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