The study of BRAFV600E expression in primary and metastatic melanoma samples
Spain (IFMSA-SPAIN)-University Complutense of Madrid, Madrid
Department of Pathology - Hospital Universitario 12 de Octubre
Dr. Jose Luis Rodriguez Peralto
Dr. Jose Luis Rodriguez Peralto, Dr. Erica Riveiro and Dr. Maria Garrido
Required: English, Accepted: Spanish
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
Yes Yes Yes Yes Yes No No No No Yes Yes No
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
The new era of targeted therapies has allowed the increase of treatment efficacy with less toxicity in oncologic patients. One of the requirements for a superior response of this type of therapy is the homogeneous expression of target molecules in tumors. In fact, the existence of tumoral heterogeneity could be responsible for resistances or relapses in clinical practice. The BRAF gene is the most common target for somatic mutations in melanoma patients. A point mutation in the BRAF gene (predominantly V600E) is detected in 40-60% of melanoma patients. Fortunately, after decades without news strategies for melanoma treatment, the emergence of therapies aimed to the mutated BRAFV600E oncogene showed improvement on overall and disease free survival of patients with metastatic melanoma disease. Nevertheless, an unresolved issue in oncology practice is the existence or not of BRAFV600E heterogeneity in melanoma tumors. Tumor resistance and relapses seen in most of patients treated with BRAFV600E inhibitors could be related to the heterogeneous expression of BRAFV600E in melanoma tumors.
What is the aim of the project?
Study through immunohistochemistry the pattern of BRAFV600E expression in paired samples of primary and metastatic melanomas tumors.
What techniques and methods are used?
Tissue Microarray and immunohistochemistry.
What is the role of the student?
- The tasks will be done under supervision
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
What are the tasks expected to be accomplished by the student?
- Revision of the literature and discussion of papers related to the field; Learning of Tissue Microarray and inmunohistochemistry techniques; Helping with immunohistochemical analyses; Discussion of the results. The student will learn the Tissue microarray (TMA) method. TMA is a technique that allows the simultaneous analysis of multiple individual tissue samples on a single slide whereby the conditions are homogeneous and there is a minimal destruction of the original tissue. Indeed, the possibility of bias due to non-representative tissue sections is overcomed by the presence of duplicated samples and the elevated amount of tumors analyzed.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, general pathological conferences (from Monday to Thursday) and dermatological clinic-pathological conferences (each other week).
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?
The student should have knowledge of physiology and histology.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- Pre-Medical students from the American-British system
- Boursault L; Haddad V; Vergier B; et al.Tumor Homogeneity between Primary and Metastatic Sites for BRAF Status in Metastatic Melanoma Determined by Immunohistochemical and Molecular Testing. PLoS One. 2013 Aug 20;8(8):e70826.
- Chapman PB; Hauschild A; Robert C; et al. BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16
- Colomba E; Hélias-Rodzewicz Z; Von Deimling A; et al. Detection of BRAF p.V600E mutations in melanomas: comparison of four methods argues for sequential use of immunohistochemistry and pyrosequencing. J Mol Diagn. 2013 Jan;15(1):94-100.
- Colombino M; Capone M; Lissia A; et al. BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. J Clin Oncol. 2012 Jul 10;30(20):2522-9.
- Long GV; Wilmott JS; Capper D; et al. Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma. Am J Surg Pathol. 2013. Jan;37(1):61-5.
- Wilmott JS; Menzies AM; Haydu LE; et al. BRAF(V600E) protein expression and outcome from BRAF inhibitor treatment in BRAF(V600E) metastatic melanoma. Br J Cancer. 2013 Mar 5;108(4):924-31.
- Wilmott JS; Tembe V; Howle JR; et al. Intratumoral molecular heterogeneity in a BRAF-mutant; BRAF inhibitor-resistant melanoma: a case illustrating the challenges for personalized medicine. Mol Cancer Ther. 2012 Dec;11(12):2704-8.
- Yancovitz M; Litterman A; Yoon J; et al. D. Intra- and inter-tumor heterogeneity of BRAF (V600E)mutations in primary and metastatic melanoma. PLoS One. 2012;7(1):e29336.