Der Pathologe

, Volume 34, Supplement 2, pp 214–220 | Cite as

Findet die molekulare Diagnostik Einzug in die Pankreaspathologie?

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Zusammenfassung

Die molekularen Veränderungen in soliden und zystischen Pankreastumoren sind in den letzten Jahren zunehmend charakterisiert worden. Das duktale Pankreaskarzinom zeichnet sich durch zahlreiche Punktmutationen und z. T. auch Deletionen und Amplifikationen von Genen aus, welche mindestens 13 tumorrelevante zelluläre Prozesse betreffen. Neben den 4 führenden Alterationen in den KRAS-, p53-, CDKN2a- und SMAD4-Genen gibt es zahlreiche Treibermutationen mit geringer Frequenz. Fortschritte sind bei der Subklassifikation der duktalen Pankreaskarzinome aufgrund von Genexpressionssignaturen zu verzeichnen, wobei ein KRAS-getriebener klassischer und ein KRAS-unabhängiger quasimesenchymaler Subtyp beschrieben wurden. Durch die Analyse von mRNA- und MicroRNA-Expressionsprofilen aus Punktaten ist die Grundlage für eine präoperative Artdiagnose von Pankreasraumforderungen geschaffen worden.

Die 4 häufigsten zystischen Pankreastumoren besitzen z. T. entitätsspezifische genetische Veränderungen, wie z. B. GNAS-Mutationen in intraduktal papillär muzinösen Neoplasien, β-Catenin-Mutationen in solidpseudopapillären Neoplasien und VHL-Punktmutationen oder „loss of heterozygosity“ in serösen Zystadenomen. Da die Zystenflüssigkeiten aus zystischen Pankreastumoren diagnostisch verwertbare DNA enthalten, besteht die Möglichkeit einer verbesserten präoperativen Unterscheidung der zystischen Pankreastumoren aufgrund von Mutationsanalysen. Zusätzlich zu DNA-basierten Verfahren gibt es viel versprechende Ansätze für die präoperative Unterscheidung benigner und prämaligner/maligner zystischer Pankreastumoren aufgrund von MicroRNA-Signaturen.

In den letzten Jahren wurden wichtige Fortschritte bei der molekularen Charakterisierung der Pankreastumoren und hinsichtlich der Methodik der präoperativen molekularen Analyse erzielt. Diese Ergebnisse geben uns Hoffnung, dass präoperative molekulare Verfahren die prognostische/therapeutische Stratifizierung duktaler Pankreaskarzinome und eine sichere präoperative Diagnostik benigner zystischer Pankreastumoren in der Zukunft ermöglichen.

Schlüsselwörter

Pankreas Duktales Adenokarzinom Molekulare Pathologie Intraduktale papilläre muzinöse Neoplasie Seröses Zystadenom 

Will molecular diagnostics become established in pancreatic pathology?

Abstract

Genetic alterations of solid and cystic tumors of the pancreas have been increasingly more characterized over the last few years. Pancreatic ductal adenocarcinoma (PDAC) carries numerous point mutations and, to a lesser extent, deletions and amplifications of genes that are associated with at least 13 tumor relevant signalling pathways and processes. Besides the four common driver mutations in the KRAS, p53, CDKN2a and SMAD4 genes there are a number of low frequency driver mutations. The classification of PDAC subtypes has benefited from recent analyses of transcriptional profiles that revealed a classical KRAS driven and a KRAS independent quasi-mesenchymal subtype. The analyses of mRNA and miRNA expression profiles of fine needle aspirates serve as a basis for reliable preoperative diagnosis of pancreatic masses.

The four most common cystic pancreatic tumors bear tumor-specific genetic alterations, such as GNAS mutations in intraductal papillary mucinous neoplasms, β-catenin mutations in solid pseudopapillary neoplasms and VHL mutations or loss of heterozygosity in serous cystadenoma. Recovery of DNA from aspirates of cyst fluids enables an improved preoperative management of cystic pancreatic tumors by mutational analysis. In addition to the analysis of DNA there are promising approaches in distinguishing benign and premalignant/malignant cystic tumors by evaluating miRNA profiles.

In recent years much progress has been made in molecular genetic characterization and preoperative evaluation of pancreatic tumors. Hopefully these results will contribute to prognostic and therapeutic stratification of PDAC and to a reliable preoperative diagnostics of benign cystic pancreatic tumors in the future.

Keywords

Pancreas Ductal adenocarcinoma Molecular pathology Intraductal papillary mucinous neoplasm Serous cystadenoma 
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Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. B. Sipos und J. Sperveslage geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Allgemeine Pathologie und Pathologische Anatomie, Institut für Pathologie und NeuropathologieUniversitätsklinikum TübingenTübingenDeutschland

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