Molekulare Marker in der Feinnadelbiopsie der Schilddrüse – ein Update

Zusammenfassung

Ziele: Die Anzahl der Schilddrüsenoperationen in Deutschland hat in den letzten Jahren signifikant um etwa 30% abgenommen. Unverändert stellt jedoch neben lokalen Beschwerden oder einer Autonomie die „diagnostische“ Schilddrüsenoperation zum Malignitätsausschluss eine wesentliche Operationsindikation dar. Dennoch wird bei einer überwiegenden Anzahl der Patienten trotz eines klinisch und/oder bildgebend verdächtigen Befunds eine präoperative Feinnadelpunktion nicht durchgeführt, da die punktionszytologische Beurteilung von der Erfahrung des Zytologen abhängig ist und nicht selten zu indifferenten Befunden führt.

Methoden: Das molekulargenetische Profiling von Feinnadelbiopsien (FNB) der Schilddrüse wird zur Verbesserung der Sensitivität und Spezifität der zytologischen Untersuchung in zunehmendem Umfang eingesetzt. Die derzeit national und international angebotenen Testverfahren werden dargestellt und bewertet.

Ergebnisse: Die molekulargenetische Analyse von Feinnadelpunktaten ist in den letzten Jahren methodisch deutlich verbessert worden. Während die Analyse in der Vergangenheit überwiegend auf spezifischen genetischen Markern basierte, ermöglichen neue Verfahren die Bestimmung umfangreicher Genpanels und Expressionsmuster. Zwischenzeitlich werden 6 kommerziell erhältliche Assays in den USA angeboten und flächendeckend eingesetzt. Auch in Deutschland werden zunehmend spezifische molekulare Panels verwendet. Die Qualität der Analysen wird für wenige Marker im Rahmen von Ringversuchen kontrolliert. Mittels Next Generation Sequencing kann in naher Zukunft auch in der Routinediagnostik eine vollständige molekulargenetische Charakterisierung erfolgen.

Schlussfolgerung: Methodik und Zielsetzung der verwendeten Verfahren unterscheiden sich deutlich. Eine kontinuierliche Standardisierung, Qualitätskontrolle und Validierung der unterschiedlichen Analyse-Verfahren ist erforderlich, um valide und vergleichbare Ergebnisse zu erzielen. Die Interpretation der Ergebnisse setzt die Kenntnis der molekulargenetischen Grundlagen der Schilddrüsenkarzinome und Besonderheiten der untersuchten Patientengruppe voraus. Momentan stellt nur der validierte Nachweis der BRAF V600E-Mutation in FNB der Schilddrüse eine direkte Indikation zur Operation dar. Für alle anderen molekulargenetischen Alterationen müssen Therapieempfehlungen zur konservativen oder operativen Therapie, zum Resektionsausmaß und zur Nachsorge in naher Zukunft formuliert werden.

Abstract

Aim: The frequency of thyroid surgery has decreased about 30% in the past years in Germany. Apart from compression symptoms in the neck and node autonomy, the diagnostic resection to exclude thyroid malignancy constitutes a predominant indication for surgery. However, despite suspicious clinical and/or imaging results a preoperative fine needle biopsy (FNB) is not used in 80% of cases due to lack of cytopathological experience and therefore frequent indifferent results.

Methods: Molecular genetic profiling of thyroid FNB is increasingly used to improve sensitivity and specificity of cytological assessment. The currently available national and international assays are reviewed and assessed.

Results: The molecular genetic analysis of thyroid FNB was significantly improved in the past years. While the analysis was restricted to specific genes in the past, new methods include multiple mutation analyses as well as identification of expression patterns of encompassing gene panels. 6 commercial assays are nowadays available and used in the USA. In Germany, selected gene panels are increasingly applied. The quality of the analysis of some genetic markers is assessed in the context of certified proficiency testings. By means of next generation sequencing, molecular profiling of thyroid FNB as part of the clinical routine will be possible in the near future.

Conclusion: Aims and methods of the employed techniques vary significantly in molecular genetic analyses of thyroid FNB. A continuous standardization, quality control and validation of the different analysis methods is necessary in order to achieve valid and comparable results. Interpretation of the results requires knowledge of the molecular genetic background of thyroid cancer in general and of the particularities of the examined patient cohort. Nowadays, only the detection of the BRAF V600E mutation in FNB with a validated laboratory method directly translates into indication for thyroid surgery. For all other detected molecular genetic alterations, recommendations for the conservative or surgical therapy, for the extent of thyroid resection, and follow-up of patients need to be developed in the near future.

Schlüsselwörter

Schilddrüse - Feinnadelbiopsie - Molekulargenetik

Key words

thyroid - fine needle biopsy - molecular genetics

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