| Title |
In situ detection of HER2:HER2 and HER2:HER3 protein–protein interactions demonstrates prognostic significance in early breast cancer
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, June 2011
|
| DOI | 10.1007/s10549-011-1606-z |
| Pubmed ID | |
| Authors |
Melanie Spears, Karen J. Taylor, Alison F. Munro, Carrie A. Cunningham, Elizabeth A. Mallon, Chris J. Twelves, David A. Cameron, Jeremy Thomas, John M. S. Bartlett |
| Abstract |
HER2 overexpression/amplification is linked with poor prognosis in early breast cancer. Co-expression of HER2 and HER3 is associated with endocrine and chemotherapy resistance, driven not simply by expression but by signalling via HER2:HER3 or HER2:HER2 dimers. Proximity ligation assays (PLAs) detect protein-protein complexes at a single-molecule level and allow study of signalling pathways in situ. A cohort of 100 tumours was analyzed by PLA, IHC and FISH. HER complexes were analyzed by PLA in a further 321 tumours from the BR9601 trial comparing cyclophosphamide, methotrexate and fluorouracil (CMF) with epirubicin followed by CMF (epi-CMF). The relationships between HER dimer expression and RFS and OS were investigated, and multivariate regression analysis identified factors influencing patient prognosis. PLA successfully and reproducibly detected HER2:HER2 and HER2:HER3 protein complexes in vivo. A significant association (P < 0.00001) was identified between HER2 homodimerization and HER2 gene amplification. Following a minimum p value approach high levels of HER2:HER2 dimers were significantly associated with reduced relapse-free (RFS; hazard ratio = 1.72, 95% confidence interval 1.15-2.56, P = 0.008) and overall survival (OS HR = 1.69 95% CI = 1.09-2.62, P = 0.019). Similarly, high levels of HER2:HER3 dimers were associated with reduced RFS (HR = 2.18, 95% CI = 1.46-3.26, P = 0.00016) and OS (HR = 2.21, 95% CI = 1.41-3.47, P = 0.001). This study demonstrates that in situ detection of HER2 and HER2:3 protein:protein complexes can be performed robustly and reproducibly in clinical specimens, provides novel prognostic information and opens a significant novel opportunity to probe the clinical impact of cellular signalling processes. |
Mendeley readers
The data shown below were compiled from readership statistics for 119 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 3% |
| Denmark | 1 | <1% |
| Ireland | 1 | <1% |
| Unknown | 114 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 24 | 20% |
| Student > Bachelor | 23 | 19% |
| Researcher | 22 | 18% |
| Student > Master | 10 | 8% |
| Other | 7 | 6% |
| Other | 17 | 14% |
| Unknown | 16 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 31 | 26% |
| Biochemistry, Genetics and Molecular Biology | 23 | 19% |
| Medicine and Dentistry | 18 | 15% |
| Engineering | 13 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
| Other | 12 | 10% |
| Unknown | 19 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 March 2014.
All research outputs
#20,223,099
of 22,747,498 outputs
Outputs from Breast Cancer Research and Treatment
#4,104
of 4,651 outputs
Outputs of similar age
#103,663
of 111,689 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#66
of 66 outputs
Altmetric has tracked 22,747,498 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,651 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 111,689 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.