The role of AP-2 alpha in predicting response to chemotherapy in breast cancer patients


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Etat: Serval
Version: Après imprimatur
ID Serval
(Mémoire de) maîtrise (master)
The role of AP-2 alpha in predicting response to chemotherapy in breast cancer patients
Université de Lausanne, Faculté de biologie et médecine
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Breast cancer is the most frequent cancer occurring in women in Europe1. In Switzerland, the incidence in 2009 was 32,9% and it was the primary cause of cancer related death in women, with a mortality rate of 19.2%2.
The management of this cancer depends on clinical data, morphology of the tumour and its molecular profile3, 4. Five different subclasses have been described using molecular profiling: luminal A, luminal B, normal-like tumour, HER2+ and basal like4, 5. Luminal A is less aggressive than HER2+5. However, it was noticed that some patients had far worse outcomes than predicted when based on molecular criteria5.
It is thought that breast cancer arises through a series of molecular alterations at the cellular level, resulting in the evasion of growth-inhibiting signals, evasion of apoptosis and spread of breast epithelial cells4. The human transcription factor and tumour suppressor activator-protein 2 (AP-2) was found to have a central role in the development of breast cancer6,7. Decrease of intracellular AP-2 is associated with more aggressive cancer types6,7.
It is possible to study AP-2 levels via new method called protein-binding microarray (PBM)7. DNA-binding protein, as AP-2, is put in contact with double stranded DNA sequences fixed on a microarray8. This technique allowed the detection of protein binding on specific DNA sequences8. This method has been demonstrated to be reliable and highly sensitive7. In an initial study done at the University of Lausanne, it was demonstrated that AP-2 binding on DNA could have a better predictive value than classic molecular diagnosis and may redistribute the subtype classification. Now, there is a need to repeat this trial with more breast cancer specimens and a more robust microarray.
My primary objective is to select 100 appropriate specimens from the pathology institute to repeat the trial. Specimens would be of the different subtype and also from tissue next to the tumour. For comparison we will also use tissue from reduction mammoplasties, as a healthy control. These specimens are obtained after either mastectomy or tumorectomy for the pathological tissue and after mammary reduction for the healthy control. All tissues samples were flash frozen and preserved at -80 C° to protect the cell proteins. Specimens and documentations will be rendered anonymously before processing by the lab.
Secondly, the specimens will be used in the PBM microarray. The result will be analysed in conjunction with clinical history and follow-up of the patient.
In conclusion, the use of PBM technique with the AP-2 protein is promising in order to improve the diagnosis of breast cancer. Using this technique we expected to better describe and understand breast cancer and the action of the tumour itself. This might lead to better prognosis of the disease and even lead to new treatment development.
Création de la notice
01/06/2012 15:36
Dernière modification de la notice
03/03/2018 17:10
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