Abstract
Conventional histology failed to classify part of non-medullary thyroid lesions as either benign or malignant. The group of tumours of uncertain malignancy (T-UM) concerns either atypical follicular adenomas or the recently called ‘tumours of uncertain malignant potential’. To refine this classification we analysed microarray data from 93 follicular thyroid tumours: 10 T-UM, 3 follicular carcinomas, 13 papillary thyroid carcinomas and 67 follicular adenomas, compared to 73 control thyroid tissue samples. The diagnosis potential of 16 selected genes was validated by real-time quantitative RT–PCR on 6 additional T-UM. The gene expression profiles in several groups were examined with reference to the mutational status of the RET/PTC, BRAF and RAS genes. A pathological score (histological and immunohistochemical) was estimate for each of the T-UM involved in the study. The correlation between the T-UM gene profiles and the pathological score allowed a separation of the samples in two groups of benign or malignant tumours. Our analysis confirms the heterogeneity of T-UM and highlighted the molecular similarities between some cases and true carcinomas. We demonstrated the ability of few marker genes to serve as diagnosis tools and the need of a T-UM pathological scoring.
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Acknowledgements
We thank Marielle Mello, Dominique Couturier and Anne Coutoleau for technical help and data processing. We thank Kanaya Malkani for the critical reading of this paper. This work was supported by grants from the French Ministry of Research, the French National Institute for Medical Research (INSERM), the University Hospital of Angers and the University of Angers (PHRC 03-10).
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Fontaine, JF., Mirebeau-Prunier, D., Franc, B. et al. Microarray analysis refines classification of non-medullary thyroid tumours of uncertain malignancy. Oncogene 27, 2228–2236 (2008). https://doi.org/10.1038/sj.onc.1210853
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DOI: https://doi.org/10.1038/sj.onc.1210853
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