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Advanced target therapies in breast cancer
Spain (IFMSA-SPAIN)-University of Santiago de Compostela, Santiago de Compostela
Pathology , Clinical Hosp and Research Group of the Health Research Institute(IDICHUS
Dr. Jose Ramon Antunez Lopez
Dr. Tomas Garcia-Caballero, Beatriz Fernandez Rodriguez and Jose Ramon Antunez Lopez
English, Spanish French
Type of Research Project
- Basic science
What is the background of the project?
Breast cancer represents the first cause of cancer mortality in women. Each year 1.151.000 new cases are diagnosed around the world and more than 400,000 women die of breast cancer. The number of new cases in Spain is 16,000/year and this cancer causes 6,000 deaths/year. The management of breast cancer has been dramatically changed with the advent of widespread screening programs and the systematic use of adjuvant hormonal therapy and chemotherapy. Recent data have shown that these changes are having a major impact in outcome, and despite increasing incidence, breast cancer mortality is decreasing in most of the Western world.
Topoisomerase 2 alpha (TOP2A) is a key enzyme in DNA metabolism. It catalyzes transient double-strand breaks that resolve the topological problems of DNA during transcription, recombination, replication and chromosome partitioning. TOP2A gene, located at 17q11.2-12, is the target for anthracyclines, but the predictive value of TOP2A or HER2 determination for benefit of anthracycline-based therapy in breast cancer is controversial. However, recent studies demonstrated that HER2/TOP2A coamplification, not HER2 amplification, is associated with responsiveness to anthracycline-containing regimens. The gold standard technique to evaluate gene status for target therapy selection is fluorescence in situ hybridization (FISH), but this technique has some disadvantages (e.g., the evaluation of tissue morphology is difficult in dark field and the fluorescence signal fades relatively quickly, making long term archiving of slides impossible). DuoCISH method is a simple extension of the FISH protocol that allows bright field microscopy evaluation of slides with the benefit that morphological features can be observed, and that archiving of slides is possible. In a recent study we showed that DuoCISH is a reliable and robust method for HER2 testing in breast cancer. Comparison between FISH and DuoCISH assays for TOP2a determination in breast carcinoma was also reported, with perfect correlation between both techniques. However, a small number of cases were included in this study.
What is the aim of the project?
1. To get the students familiar with immunohistochemical and in situ hybridization techniques applied to predict response to target therapies in breast cancer. 2. To compare the results obtained with FISH and DuoCISH for determination of TOP2A gene status in larger series studying both complete sections and tissue microarrays.
What techniques and methods are used?
Immunohistochemical determination, fluorescence in situ hybridization.
What is the role of the student?
What are the tasks expected to be accomplished by the student?
The student participate in regular research task at the laboratory and be in contact with pathology diagnostic reality. . It is expected that students could work independently in the lab and develop the capacity to carry out the experiments by themselves. The student will learn basic understanding and knowledge about immunohistochemical and in situ hybridization techniques.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Minimal knowledge of lab routine (for example: solution preparation, calculate concentrations
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Press MF; Sauter G; Buyse M; Bernstein L; Guzman R; Santiago A; Villalobos IE; Eiermann W; Pienkowski T; Martin M; Robert N; Crown J; Bee V; Taupin H; Flom KJ; Tabah-Fisch I; Pauletti G; Lindsay MA; Riva A; Slamon DJ. Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol. 2011; 29:859-67
- García-Caballero T; Grabau D; Green AR; Gregory J; Schad A; Kohlwes E; Ellis IO; Watts S; Mollerup J. Determination of HER2 amplification in primary breast cancer using dual-colour chromogenic in situ hybridization is comparable to fluorescence in situ hybridization: a European multicentre study involving 168 specimens. Histopathology. 2010; 56:472-80.
- Santiago MP; Vázquez-Boquete A; Fernández B; Masa C; Antúnez JR; Fraga M; Forteza J; García-Caballero T. Whether to determine HER2 status for breast cancer in the primary tumour or in the metastasis. Histol Histopathol.
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