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Epithelial-mesenchymale Transition beim nichtkleinzelligen Bronchialkarzinom

Epithelial−mesenchymal transition in non-small cell lung cancer

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Zusammenfassung

Das nichtkleinzellige Bronchialkarzinom (NSCLC) ist ein stark fibrosierender Tumor mit Ausbildung eines prominenten desmoplastischen Stromas. Die epithelial-mesenchymale Transition (EMT) ist eine der Hauptinvasionsarten. Mittels Massenspektrometrie identifizierten wir das stromale N-Glykoprotein Periostin in Pleuraergüssen von Lungenadenokarzinomen. Die immunhistochemische Validierung auf einem NSCLC-Tissue-Microarray sowie auf Großschnitten zeigte, dass Periostin an der Invasionsfront stark aufreguliert wird, sowohl in den Tumorepithelien als auch im umgebenden matrizellulären Stroma. Im Vergleich zu Kollagen, Elastin oder Vimentin war Periostin am engsten assoziiert mit Parametern der Progression, wie größerer Tumor oder höheres Stadium, mit dem Plattenepithelkarzinom und mit schlechterem Überleben. Eine Assoziation mit Letzterem wurde auch für das Zelladhäsionsmolekül L1CAM gefunden. Zusammenfassend kann gesagt werden, dass das NSCLC-Wachstum assoziiert ist mit vermehrter Stromabildung und Aufregulation von EMT-Markern an der Invasionsfront. Die Invasionsfront könnte eine topographisch wichtige Region für eine zielgerichtete Therapie gegen Stroma oder EMT sein.

Abstract

Non-small cell lung carcinoma (NSCLC) is a highly fibrotic malignancy, which exhibits a prominent desmoplastic stroma. Epithelial–mesenchymal transition (EMT) is one of the main modes of carcinoma invasion. We identified the stromal N-glycoprotein periostin by mass spectrometry of lung adenocarcinoma pleural effusions. Validation on a NSCLC tissue microarray and on tumor whole sections by immunohistochemistry indicated that periostin is strongly upregulated at the invasive front in both tumor epithelia and the surrounding matricellular space. In comparison to collagen, elastin and vimentin, periostin was found to be most closely associated with parameters of tumor progression such as larger size and higher stage, with the squamous cell histotype, and with decreased survival. An association with decreased survival was also found for the cell adhesion molecule L1CAM. In conclusion, enlargement of NSCLC tumors is associated with an increase of desmoplastic stroma and concomitant upregulation of EMT markers at the invasive front. The tumor–stroma interface may be a candidate topographic region for stroma- or EMT-directed therapy.

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  1. Institut für Klinische Pathologie, Universitätsspital Zürich, Schmelzbergstr. 12, 8091, Zürich, Schweiz

    A. Soltermann

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Soltermann, A. Epithelial-mesenchymale Transition beim nichtkleinzelligen Bronchialkarzinom. Pathologe 33 (Suppl 2), 311–317 (2012). https://doi.org/10.1007/s00292-012-1635-3

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  • DOI: https://doi.org/10.1007/s00292-012-1635-3

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