Molecular and mutational profiling in Papillary Thyroid Carcinoma with special emphasis on the influence of BRAFV600E Mutation on Tumor Stage, Outcome and nuclear imaging

Completed · 2011 until 2013

Clinical Studies
Monocentric project at KSSG
Start Date
End Date
Study Design
Prof. Dr. med. S.J. Stöckli, HNO KSSG PD Dr. med. M. Brändle, Endokrinologie KSSG Dr. med. St. Bilz, Endokrinologie KSSG Dr. med. T. Clerici, Chirurgie KSSG Dr. med. R. Oettli, Nuklearmedizin KSSG Dr. med. J. Müller, Nuklearmedizin KSSG Prof. Dr. med. W. Jochum, Pathologie KSSG S.R. Haile, PhD, statistician CTU KSSG Prof. Ralph Schlapbach, Managing Director, Functional Genomics Center Zurich
Brief description/objective

Background: The optimal treatment of papillary thyroid carcinoma (PTC) is still a matter of debate, despite the usually excellent prognosis of patients with this tumor type. Markers are needed to identify patients with high risk of recurrence. The BRAFV600E mutation is the most frequent genetic alteration in PTC and has been reported in 30-80% of PTC. BRAFV600E mutations have been associated with aggressive tumor characteristics, including extrathyroidal extension, lymph node involvement, and recurrence. Furthermore BRAF mutations in PTC are associated with impaired radioiodine (131I) but increased 18F-fluorodeoxyglucose (FDG) uptake due to a low expression of thyroid-related genes and a high expression of glucose type-1 (Glut-1) transporter gene. Although there are different studies indicating the prognostic importance and the role for follow up procedures of patients diagnosed with PTC, these findings until now do not have any implication on therapeutic strategies and management of patients.
Objective: To establish a database of a large cohort of PTC (250 patients who were treated at the Kantonsspital St.Gallen between 1990 and 2010) with demographic data, histopathological tumor characteristics, staging, treatment regimen and clinical follow-up within an interdisciplinary research group. To set up a tissue microarray (TMA) and a DNA biobank of the PTCs. Evaluation of the prevalence and prognostic significance of the BRAFV600E mutation in the cohort of PTC, and correlating the presence of the mutation with clinicopathological features such as gender, age, T-and N-stage and extrathyroidal extension as well as tumor control rate of patients with PTC.
Analysis of the role of BRAFV600E mutation on Glut-1 expression and its influence on nuclear imaging such as 131I and 18F-FDG-PET scan. Based on this database a prospective trial concerning the value of BRAFV600E mutation detection in fine needle aspiration biopsies is planned in order to screen patients needing more advanced treatment regimen preoperatively.
To extend this research project on detailed molecular profiling and to define further useful biomarkers of PTC, research collaboration has been established with Prof. Ralph Schlapbach, Managing Director of the functional genomics center in Zurich, a competence center in the areas of genomics, transcriptomics, proteomics, and metabolomics. Based on the results we will perform a prospective trial concerning the value of these biomarkers in FNAB. Moreover we will perform follow-studies about the role of genetic alterations in other genes for clinical staging and prognosis. For these studies an application for research funding by the Swiss National Science Foundation will be submitted.