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Neue Einblicke in die Entstehung des Pankreaskarzinoms

Die Rolle der atypischen flachen Läsionen in der Karzinogenese

New insights into the origin of pancreatic cancer

Role of atypical flat lesions in pancreatic carcinogenesis

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Zusammenfassung

Die Identifizierung und Charakterisierung von Krebsvorläuferläsionen hat bei verschiedenen malignen Neoplasien die Entwicklung von Screeningprogrammen ermöglicht, mit deren Hilfe die Mortalitätsrate reduziert werden konnte. Dies gilt bislang nicht für das pankreatische duktale Adenokarzinom (PDAC), das nach wie vor klinisch erst erkannt wird, wenn es invasiv geworden ist. Um die Entwicklung diagnostischer Verfahren zur Früherkennung des PDAC zu ermöglichen, ist eine genaue Kenntnis seiner Vorläuferläsionen notwendig. Die häufigste bislang bekannte Vorläuferläsion ist die pankreatische intraepitheliale Neoplasie (PanIN), die einen duktalen Phänotyp zeigt und einen duktalen Ursprung des PDAC nahe legt. Genetisch konstruierte Mausmodelle des PDAC zeigen jedoch, dass außer PanIN auch tubuläre Zellkomplexe (TC) zentroazinären Ursprungs durch eine azinär-duktale Metaplasie (ADM) atypische flache Läsionen (AFL) als alternative Vorläufer des PDAC ausbilden können. Die TC, AFL und murinen PanIN wurden von uns im Mausmodell eingehend morphologisch und molekulargenetisch charakterisiert und mit den menschlichen Pankreasläsionen verglichen. Auf der Basis unserer Befunde stellen wir ein duales Modell der Entwicklung des PDAC vor, das die Rolle der AFL als Vorläuferläsion berücksichtigt.

Abstract

The identification and characterization of precursor lesions is fundamental to develop screening programs for early diagnosis and treatment, aiming at reducing cancer-related mortality. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that becomes clinical apparent only in advanced stages. In order to enable screening procedures for early detection of PDAC, an exact characterization of precursor lesions is of utmost importance. Pancreatic intraepithelial neoplasias (PanIN) are the most frequent and best characterized precursors of PDAC and are lesions with a ductal phenotype thus indicating a ductal cell origin of PDAC. However, evidence from genetically engineered mouse models suggests that tubular complexes (TC) originating through a process of acinar-ductal metaplasia (ADM) form atypical flat lesions (AFL) that may represent an alternative pathway of pancreatic carcinogenesis. Based on a thorough morphological and genetic analysis of murine TC, AFL and PanIN and their human counterparts, a new dual model of pancreatic carcinogenesis is proposed taking into account the role of AFL as possible new precursors of PDAC.

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Authors and Affiliations

  1. Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Trogerstr. 18, 81675, München, Deutschland

    I. Esposito, B. Konukiewitz, A.M. Schlitter & G. Klöppel

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  1. I. Esposito
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  2. B. Konukiewitz
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  3. A.M. Schlitter
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  4. G. Klöppel
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Correspondence to I. Esposito.

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Esposito, I., Konukiewitz, B., Schlitter, A. et al. Neue Einblicke in die Entstehung des Pankreaskarzinoms. Pathologe 33 (Suppl 2), 189–193 (2012). https://doi.org/10.1007/s00292-012-1673-x

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