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Form follows function: Morphological and immunohistological insights into epithelial-mesenchymal transition characteristics of tumor buds.

  • Enderle-Ammour K 1 Institute for Surgical Pathology, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Bader M 2 Department of Reconstructive Surgery, Division of Cranio-Maxillo-Facial Surgery, University of Basel, Basel, Switzerland.
  • Ahrens TD 1 Institute for Surgical Pathology, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Franke K 3 Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg, Campus Giessen, Giessen, Germany.
  • Timme S 1 Institute for Surgical Pathology, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Csanadi A 1 Institute for Surgical Pathology, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Hoeppner J 4 Clinic for General and Visceral Surgery, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Kulemann B 4 Clinic for General and Visceral Surgery, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Maurer J 4 Clinic for General and Visceral Surgery, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Reiss P 6 Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Schilling O 5 German Cancer Consortium (DKTK) and Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Keck T 9 Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
  • Brabletz T 10 Department of Experimental Medicine I, Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Erlangen, Germany.
  • Stickeler E 11 Comprehensive Cancer Center Freiburg, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Werner M 1 Institute for Surgical Pathology, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Wellner UF 9 Clinic for Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
  • Bronsert P 1 Institute for Surgical Pathology, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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  • 2017-05-06
Published in:
  • Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - 2017
EMT
Tumor budding
ZEB1
three dimensional tumor reconstruction
Adenocarcinoma
Cadherins
Cell Line, Tumor
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Regression Analysis
Signal Transduction
Zinc Finger E-box-Binding Homeobox 1
English In cancer biology, the architectural concept "form follows function" is reflected by cell morphology, migration, and epithelial-mesenchymal transition protein pattern. In vivo, features of epithelial-mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial-mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial-mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial-mesenchymal transition marker expression were assessed for each tumor cell. Epithelial-mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial-mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial-mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that the epithelial-mesenchymal transition zinc finger E-box-binding homeobox 1-E-Cadherin cascade is initiated by zinc finger E-box-binding homeobox 1, our results are contrary and outline other possible pathways influencing the regulation of E-Cadherin.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/231971
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