L1CAM/CD171 expression in human tumors and its association with tumor phenotype

Authors

  • Seyma Büyücek Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Magalie Lurati Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Katharina Möller Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Florian Fiehweger Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Ria Schlichter Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Anne Menz Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Andreas M Luebke Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Viktor Reiswich Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Martina Kluth Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Claudia Hube-Magg Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Andrea Hinsch Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Florian Lutz Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Sören Weidemann Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Frank Jacobsen Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • David Dum Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Christian Bernreuther Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Patrick Lebok Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
  • Guido Sauter Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Andreas H. Marx Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
  • Ronald Simon Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Christoph Fraune Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
  • Natalia Gorbokon Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Eike Burandt Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Sarah Minner Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Stefan Steurer Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Till S Clauditz Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Till Krech Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
  • Viktoria Chirico Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Maximilian Lennartz Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

DOI:

https://doi.org/10.2340/1651-226X.2025.43587

Keywords:

L1CAM, cell adhesion molecules, biomarkers, tumor, membrane proteins, tissue array analysis, immunohistochemistry

Abstract

Background and purpose: L1CAM (CD171) is suggested to play a critical role in cancer. Because of its expression in only few normal tissues and its membranous nature, L1CAM is a promising drug target.

Patient/material and methods: To clarify the role of L1CAM expression in different cancer types, a tissue microarray containing 20,079 samples from 135 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

Results: Membranous L1CAM staining was found in 1,175 (9.1%) of 12,888 interpretable tumor samples, including 301 (2.3%) with weak, 569 (4.4%) with moderate, and 305 (2.4%) with strong positivity. 74 of 135 tumor entities showed L1CAM staining, and 36 tumor categories included at least one case with strong L1CAM staining. The frequency of L1CAM positivity was high in subtypes of neural and neuroendocrine neoplasms (up to 100%), endometrium carcinoma (24.1-31.3%), ovarian cancer (10.0-33.1%), cervical adenocarcinoma (9.1%), malignant melanoma (24.1-31.3%), malignant mesothelioma (16.7-20.8%), adenocarcinomas of the gastrointestinal and biliopancreatic tract (4.9-14.1%), and in urothelial tumors (up to 10.3%). High L1CAM expression was associated with invasive tumor growth (pTa vs. pT2-4) in urothelial carcinoma of the bladder (p<0.0001) and with mismatch repair deficiency in colorectal adenocarcinoma (p=0.0064). However, L1CAM staining was unrelated to tumor phenotype in seven other tumor entities.

Interpretation: The results highlighted a small number of tumor entities that could be targeted by anti-L1CAM drugs, once these are proved to be sufficiently safe and efficient. L1CAM expression does not appear to confer an aggressive phenotype to affected cancer cells.

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2025-12-02

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Büyücek, S., Lurati, M., Möller, K., Fiehweger, F., Schlichter, R., Menz, A., … Lennartz, M. (2025). L1CAM/CD171 expression in human tumors and its association with tumor phenotype. Acta Oncologica, 64, 1621–1630. https://doi.org/10.2340/1651-226X.2025.43587

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Copyright (c) 2025 Seyma Büyücek, Magalie Lurati, Katharina Möller, Florian Fiehweger, Ria Schlichter, Anne Menz, Andreas M Luebke, Viktor Reiswich, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Florian Lutz, Sören Weidemann, Frank Jacobsen, David Dum, Christian Bernreuther, Patrick Lebok, Guido Sauter, Andreas H. Marx, Ronald Simon, Christoph Fraune, Natalia Gorbokon, Eike Burandt, Sarah Minner, Stefan Steurer, Till S Clauditz, Till Krech, Viktoria Chirico, Maximilian Lennartz

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