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Erschienen in: Virchows Archiv 6/2020

01.06.2020 | Original Article

Atypical goblet cell hyperplasia occurs in CPAM 1, 2, and 3, and is a probable precursor lesion for childhood adenocarcinoma

verfasst von: Fabian Fakler, Umut Aykutlu, Luka Brcic, Sylvia Eidenhammer, Andrea Thueringer, Karl Kashofer, Janina Kulka, Wim Timens, Helmut Popper

Erschienen in: Virchows Archiv | Ausgabe 6/2020

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Abstract

Congenital pulmonary airway malformation (CPAM) is a developmental disorder. Types 1-2-3 are the more common ones. Atypical goblet cell hyperplasia (AGCH) in CPAM might be a precursor lesion for pulmonary adenocarcinomas. In nine out of 33 CPAM cases, types 1–3 showed foci of goblet cell proliferations. As these cells completely replace normal epithelium, we prefer to name these proliferations AGCH. In 5 cases, adenocarcinomas were seen (AC). All cases were analyzed for proteins possibly being associated with CPAM development: fibroblast growth factor 10 (FGF10) and receptor 2 (FGFR2), forkhead box A1 (FOXA1) and A2 (FOXA2), MUC protein 5AC (MUC5AC), human epidermal growth factor receptor 2 (erbB2, HER2/neu), hepatocyte nuclear factor 4α (HNF4α), SOX2, and Ying Yang protein 1 (YY1). By next generation sequencing, AGCH and adenocarcinomas were evaluated for driver mutations. Expression for FGF10, FGFR2, FOXA1, and FOXA2 was seen in CPAM epithelium and stroma, but not differently in AGCH and AC. SOX2 was positive in CPAM epithelium and AGCH, however weakly in AC. YY1 and MUC5AC showed more intense staining in AGCH and AC than in CPAM epithelium. HER2 was intensely expressed in AC and less intensely in AGCH, but not in CPAM epithelium. KRAS mutation in exon 2 was detected in all AGCH and AC, but was absent in CPAM epithelia. AGCH can arise in CPAM types 1–3. Oncogenic KRAS mutation seems to be the oncogenic driver already in AGCH, proving its role as a precursor lesion for adenocarcinoma. It might upregulate HER2 at the protein level. YY1 seems to be involved in carcinogenesis.
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Metadaten
Titel
Atypical goblet cell hyperplasia occurs in CPAM 1, 2, and 3, and is a probable precursor lesion for childhood adenocarcinoma
verfasst von
Fabian Fakler
Umut Aykutlu
Luka Brcic
Sylvia Eidenhammer
Andrea Thueringer
Karl Kashofer
Janina Kulka
Wim Timens
Helmut Popper
Publikationsdatum
01.06.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 6/2020
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-019-02732-4

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