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Master Thesis

Pathologie moléculaire des carcinomes anaplasiques thyroïdiens : étude rétrospective à propos de 144 cas

Abstract : Introduction: Anaplastic thyroid carcinoma (ATC) is a rare tumor with poorly defined oncogenic molecular mechanisms, thereby limiting therapeutic options and contributing to its poor prognosis. The aim of this retrospective study was to determine the frequency of ALK translocations and identify the mutational profile of ATC. Materials and methods: 144 cases were collected. FISH (Fluorescence in situ hybridization) and immunohistochemistry (IHC) analysis were performed on Tissue Micro Arrays. FISH or IHC positive cases were then screened for fusion transcripts by RT-PCR. A panel of 50 genes was also screened for mutations using next generation sequencing (NGS). Results: FISH was interpretable for 90 cases (62.5%). 1 case (1.1%) was positive for an ALK rearrangement with a borderline FISH threshold (15%) but was negative upon IHC analysis and no fusion transcript (ALK-STRN nor ALK-EML4) was identified using RT-PCR. 3 cases (2.1%) ! showed positive IHC (2+) staining without a FISH rearrangement. NGS results were interpretable for 94 cases (65.3%); 42.6% harbored a mutation of the RAS genes, 13.8% had a BRAF mutation, 17% displayed a PI3K-AKT pathway mutation, 7.4% showed both RAS and PI3K pathway mutations and 3% harbored both TP53 and PTEN mutations. TP53 mutations were the most frequent (57.5%). 18.1% of cases showed no mutations of the RAS or PI3K-AKT pathways, but isolated mutations of ATM, CDKN2A, ERBB2, ALK, CPA, RET and SMAD4 were identified, including mutations not yet described in thyroid tumors. 8.5% of cases did not harbor mutations in the targeted genes nor display RET / PTC rearrangements as assessed by FISH. Conclusion: Our study confirms that ALK rearrangements in ATC are rare and that the mutational landscape of ATC is heterogeneous, involving many genes implicated in the follicular epithelial cell dedifferentiation process. The role of these mutations in thyroid oncogenesis is not fully defined at present, thus explaining the limited effectiveness of ta rgeted therapeutic options.
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Master Thesis
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Contributor : Bu Carreire Université de Bordeaux <>
Submitted on : Wednesday, December 16, 2015 - 6:09:38 PM
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  • HAL Id : dumas-01245153, version 1



Benjamin Bonhomme. Pathologie moléculaire des carcinomes anaplasiques thyroïdiens : étude rétrospective à propos de 144 cas. Médecine humaine et pathologie. 2015. ⟨dumas-01245153⟩



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