Gene expression profiling in porocarcinoma indicates heterogeneous tumor development and substantiates poromas as precursor lesions

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Svenja Holst - , University Hospital Duesseldorf (Author)
  • Anna K. Weber - , University Hospital Duesseldorf (Author)
  • Friedegund Meier - , Department of Dermatology, Skin Tumor Center, University Hospital Carl Gustav Carus Dresden (Author)
  • Jörg Otte - , University Hospital Duesseldorf, Karolinska Institutet (Author)
  • Patrick Petzsch - , Heinrich Heine University Düsseldorf (Author)
  • Julia Reifenberger - , University Hospital Duesseldorf (Author)
  • Thorsten Wachtmeister - , Heinrich Heine University Düsseldorf (Author)
  • Dana Westphal - , Department of Dermatology, Skin Tumor Center, University Hospital Carl Gustav Carus Dresden (Author)
  • Mirjana Ziemer - , Leipzig University (Author)
  • Wasco Wruck - , University Hospital Duesseldorf (Author)
  • James Adjaye - , University Hospital Duesseldorf (Author)
  • Regina C. Betz - , University of Bonn (Author)
  • Arno Rütten - , Medical care center Dermapathology Friedrichshafen/Lake Constance PartG (Author)
  • Harald M. Surowy - , University Hospital Duesseldorf (Author)
  • Silke Redler - , University Hospital Duesseldorf (Author)

Abstract

Background and objectives: Malignant sweat gland tumors are rare, with the most common being eccrine porocarcinoma (EP). Approximately 18% of benign eccrine poroma (EPO) transit to EP. Previous research has provided first insights into the mutational landscape of EP. However, only few studies have performed gene expression analyses. This leaves a gap in the understanding of EP biology and potential drivers of malignant transformation from EPO to EP. Methods: Transcriptome profiling of 23 samples of primary EP and normal skin (NS). Findings from the EP samples were then tested in 17 samples of EPO. Results: Transcriptome profiling revealed diversity in gene expression and indicated biologically heterogeneous sub-entities as well as widespread gene downregulation in EP. Downregulated genes included CD74, NDGR1, SRRM2, CDC42, ANXA2, KFL9 and NOP53. Expression levels of CD74, NDGR1, SRRM2, ANXA2, and NOP53 showed a stepwise-reduction in expression from NS via EPO to EP, thus supporting the hypothesis that EPO represents a transitional state in EP development. Conclusions: We demonstrated that EP is molecularly complex and that evolutionary trajectories correspond to tumor initiation and progression. Our results provide further evidence implicating the p53 axis and the EGFR pathway. Larger samples are warranted to confirm our findings.

Details

Original languageEnglish
Pages (from-to)1115-1124
Number of pages10
JournalJDDG - Journal of the German Society of Dermatology
Volume22
Issue number8
Publication statusPublished - Aug 2024
Peer-reviewedYes

External IDs

PubMed 38899945
ORCID /0000-0003-4340-0402/work/169643380
ORCID /0000-0003-4340-9706/work/169643428

Keywords

ASJC Scopus subject areas

Keywords

  • eccrine porocarcinoma, skin cancer, sweat gland carcinoma, transcriptome analysis