Molekulare Pathogenese von Schilddrüsenknoten – Bedeutung für die klinische Versorgung

Abstract

Thyroid nodules represent heterogeneous tumors with distinct molecular signatures. While benign thyroid nodules correspond to poly- or monoclonal tumors, thyroid carcinomas are monoclonal and thus "real" neoplasms. These are caused by somatic mutations that lead to the constitutive activation of specific signaling cascades and determine the corresponding histology and also partly the functional phenotype of the thyroid tumor. Dedifferentiation of thyroid carcinomas is accompanied by the occurrence of additional mutations in the tumors. The mutation load of thyroid carcinomas correlates with their biological behavior. In clinical practice, detection of somatic mutations can help in the cytological differential diagnosis. In the prognostic assessment of thyroid tumors, proof of classical oncogene mutations (BRAF, RAS) has little relevance. Other genetic alterations, especially TERT promoter mutations that occur with increasing frequency in advanced thyroid carcinomas, probably have a prognostic significance. The molecular signature, however, is of great relevance for the development and application of targeted therapies in advanced carcinomas (radioactive iodine-refractory DTC, PDTC and ATC, metastatic medullary carcinoma). For this, there is increasing evidence from clinical studies and case reports that underline the concept of "oncogene addiction" as a pathogenetically relevant mechanism of thyroid tumorigenesis and carcinogenesis.

Clinicopathological Significance of Overall Frequency of Allelic Loss (OFAL) in Lesions Derived from Thyroid Follicular Cell

“…On the other hand, detection of a relatively high OFAL value in NGs suggests the presence of genetically altered precursor cells preceding morphological changes in the thyroid gland. High OFAL in NG may result from its polyclonality and various aberrations in different nodules [ 53 ]. Given the significantly higher OFAL value in NG in relation to PTC in our study, we conclude that the co-occurrence of LOH/MSI at different loci predisposes to its recognition as a marker distinguishing benign lesions from malignant tumors.…”

Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine

“…RAS mutations exhibit different rates in FA: mutations in HRAS are detected in 8%, in NRAS in 6% and in KRAS in 10%, respectively [ 51 , 54 , 55 ]. Interestingly, RAS mutations have a higher prevalence in FA of persons living in area of iodine deficiency [ 56 ]. In UMP tumors, HRAS mutation are present in 3–12% of cases at codon 61, similarly to KRAS mutations (6–9% of cases), but less frequently than NRAS mutations (16–35% of cases) [ 50 , 51 , 54 , 55 ].…”

Kommentar der Schriftleitung

“…Der Artikel ist insofern lesenswert, da er sehr fundiert und praktisch nochmals die Basisuntersuchungen unseres Faches zusammenstellt. Die Übersicht beschäftigt sich mit der Sonografie von Schilddrüsenknoten [2] in einem Beitrag von Dr. Schmidt aus der Nuklearmedizin der Universität Erlangen [3]. Weiterhin ist eine hoch lesenswerte Arbeit von Frau Annette Leonhardt der Abteilung für Präventions-/ Inklusions-und Rehabilitationsforschung der LMU München, den Lehrstuhl für Gehör losen-und Schwerhörigen-Diagnostik zum Thema: "Wenn gehörlose Kinder hörend werden -Auswirkungen der CI-Versorgung von gehörlo-sen Kindern gehörloser Eltern auf deren Familiensituation" [4].…”