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Highlighting the anatomopathological features and molecular criteria of microsatellite instability (MSI) in colorectal cancers: experience of the pathological anatomy department of the Mohammed VI University Hospital in Marrakesh.
Morocco (IFMSA-Morocco), Faculty of medicine and pharmacy of Marrakech, Marrakech
Anatomical pathology department, University hospital of Marrakech
Pr. Rais Hanane
Pr. Rais Hanane, Dr. Salma Amouzoune and the department residents
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Colo-rectal cancer ranks as the fourth most common cancer in men (after lung, prostate and stomach) and the third most common in women (after breast and cervix). In Morocco, the incidence of colon cancer is estimated at 2.7 per 100,000 inhabitants per year in men and 2.2 per 100,000 inhabitants per year in women. Colorectal carcinogenesis is now well described, with two pathways, the main one being chromosomal instability in 75% of cases then comes microsatellite instability or MSI phenotype in 15% of cases. Characteristics of microsatellites instability (MSI) are abnormal variations of the number of recombinant DNA sequences from the same individual. MSI had been first described in a rare hereditary colon cancer, Lynch syndrome or HNPCC (Hereditary Non Polyposis Colon Cancer). Later, MSI was described in 15% of sporadic colon cancers. To confirm the diagnosis of MSI, a panel of five markers are used, amplified by multiplex PCR (Polymerase Chain Reaction). In sporadic cancers, MSI is the consequence of MLH1 (MutL homolog 1) silencing by epimutation of the promoter, and is correlated with a better prognosis although with a resistance to adjuvant chemotherapy.
What is the aim of the project?
The goal of our project is to highlight the anatomopathological features and molecular criteria, notably the MSI criterion, in colorectal cancer cases supported by the anatomical pathology department of the Mohammed VI University Hospital in Marrakesh, and to assess the histo-prognostic factors, by comparing it to other national and international series.
What techniques and methods are used?
- Molecular biology and Immunohistochemical methods: DNA was extracted from tumours and amplified using the PCR (Polymerase Chain Reaction); high-frequency microsatellite instability is identified based on the presence of at least two of the five instability markers in the Bethesda microsatellite panel (BAT25, BAT26, MFD15, D2S123, and D5S346), while Low-frequency microsatellite instability is identified based on the presence of only one of the mentioned instability markers. -Retrospective study of patient's files: Using the register of the department of pathological anatomy and taking into consideration: - Histopathological reports - The clinical file of the patient including the clinical observation of the patient and the para-clinical examinations at various stages of the patient's support. Data analysis and quantification will be performed using the SPSS statistical software system.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The incoming student will: -Observe and take part of the pre-analytic phase under supervision of the resident doctors: Reception, Fixation. -Observe and work on biomolecular and immunohistochemical methods under supervision. -Retrospective study and analysis of patient’s files assisted by research Phd doctors. -Work on a standardized report containing all the elements necessary for the care of patients with colorectal cancer following the MSI molecular profile.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, a training will be provided by the head of the departement on the techniques and methods used for this project.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - The student will prepare an abstract
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Knowledge in molecular biology and oncology is highly recommended.
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)
- de la Chapelle; A.; & Hampel; H. (2010). Clinical Relevance of Microsatellite Instability in Colorectal Cancer. Journal of Clinical Oncology; 28(20); 3380‑3387. https://doi.org/10.1200/JCO.2009.27.0652 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903331/
- « Accuracy of Revised Bethesda Guidelines; Microsatellite Instability; and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer. | Genetics and Genomics | JAMA | JAMA Network »; s. d. https://jamanetwork.com/journals/jama/fullarticle/200779
- A thesis of Dr. Layla BEN YOUNESS (in french): http://wd.fmpm.uca.ma/biblio/theses/annee-htm/FT/2016/these50-16.pdf
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