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

Our plain-English summary of L1CAM/CD171 expression in human tumors and its association with tumor phenotype, by S. Büyücek, M. Lurati, K. Möller, et al (Acta Oncologica, 2025).

The study

• Authors: S. Büyücek, M. Lurati, K. Möller, F. Fiehweger, R. Schlichter, A. Menz, A.M. Luebke, V. Reiswich, M. Kluth, C. Hube-Magg, A. Hinsch, F. Lutz, S. Weidemann, F. Jacobsen, D. Dum, C. Bernreuther, P. Lebok, G. Sauter, A.H. Marx, R. Simon, C. Fraune, N. Gorbokon, E. Burandt, S. Minner, S. Steurer, T.S. Clauditz, T. Krech, V. Chirico, M. Lennartz
• Journal: Acta Oncologica
• Published: 2025;64:1621-1630
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study from Germany measured how often the protein L1CAM (CD171), a possible cancer drug target, appears in human tumors. It did not study asbestos or any other exposure. The authors stained archived samples from 20,079 tumors of 135 types, plus 608 normal tissue samples, with an antibody test (immunohistochemistry). 12,888 tumor samples could be read, and 1,175 (9.1%) of these showed L1CAM staining. Rates were highest in some neural and neuroendocrine tumors (up to 100%). In mesothelioma, 16.7% of 30 readable epithelioid samples and 20.8% of 24 readable biphasic samples were positive. Both appear under a table heading for tumors of the lung, pleura and thymus, but individual case sites are not given. L1CAM was associated with invasive growth in bladder urothelial carcinoma (p less than 0.0001). In colon cancer, staining was less common in mismatch repair deficient tumors. Staining was reported as unrelated to tumor features in muscle-invasive bladder cancer and six other tumor types. The authors concluded that L1CAM can be expressed in many tumor types but is largely unrelated to cancer aggressiveness. The antibody came from a company owned by a family member of one author.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of archived tumor and normal tissue samples, stained for L1CAM by immunohistochemistry on tissue microarrays, with chi-square tests comparing staining with tumor features
• Who was studied: 20,079 primary tumors from 135 tumor types and subtypes, plus 608 normal tissue samples (8 donors for each of 76 normal tissue types), from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany. Dates of collection are not given.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study measured staining for the protein L1CAM (CD171) using the antibody MSVA-171R.
• Main results:
  • 12,888 of the 20,079 tumor samples (64.2%) could be interpreted.
  • L1CAM staining was found in 1,175 (9.1%) of the 12,888 interpretable tumor samples.
  • Positivity was highest in several subtypes of neural and neuroendocrine tumors (up to 100%).
  • Malignant mesothelioma was L1CAM positive in 16.7% to 20.8% of samples, depending on subtype.
  • Table 1 lists both mesothelioma categories under the heading for tumors of the lung, pleura and thymus. It gives no site for individual cases and has no separate peritoneal mesothelioma category.
  • Epithelioid mesothelioma: 40 on the array, 30 analyzable. 83.3% were negative, 3.3% weak, 6.7% moderate and 6.7% strong.
  • Biphasic mesothelioma: 77 on the array, 24 analyzable. 79.2% were negative, 0.0% weak, 12.5% moderate and 8.3% strong.
  • High L1CAM expression was associated with invasive growth (pTa vs pT2-4) in urothelial carcinoma of the bladder (p less than 0.0001). In colorectal adenocarcinoma it was associated with mismatch repair protein deficiency (p = 0.0064) and left-sided location (p = 0.0104).
  • In colon adenocarcinoma, 78.5% of 1,127 mismatch repair proficient tumors were L1CAM negative, compared with 92.8% of 83 mismatch repair deficient tumors (p = 0.0064).
  • L1CAM staining was reported as unrelated to tumor phenotype within muscle-invasive urothelial carcinoma, which is a subgroup of the bladder cancers above. The same was reported for six other tumor types: clear cell and papillary renal cell carcinoma, serous high-grade ovarian carcinoma, endometrioid endometrial carcinoma, gastric adenocarcinoma and pancreatic ductal adenocarcinoma.
• The authors' conclusion: The authors concluded that L1CAM can be expressed in a broad range of tumor types, but its expression level is largely unrelated to cancer aggressiveness.
• Limitations the authors state:
  • The authors noted that their test detects L1CAM on tumor cells only. Cleaved or exosomal fragments of the protein cannot be detected by this method.

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Neoplasm, Carcinoma, Ovarian Cancer, Adenocarcinoma, Mesothelioma, Mismatch Repair Deficiency (dMMR).

Related studies

• Reduced occludin expression is related to unfavorable tumor phenotype and poor prognosis in many different tumor types: A tissue microarray study on 16,870 tumors — S. Büyücek, F. Viehweger, et al. (2025)
• Prevalence of S-methyl-5'-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer: A Tissue Microarray Study on 13,067 Tumors From 149 Different Tumor Types — N. Gorbokon, N. Wößner, et al. (2024)
• Prevalence of heterozygous and homozygous 9p21 deletions in human cancer: a tissue microarray study on 4,999 tumors from 125 different tumor types — N. Gorbokon, K. Teljuk, et al. (2026)
• Stimulator of Interferon Genes Protein (STING) Expression in Cancer Cells: A Tissue Microarray Study Evaluating More than 18,000 Tumors from 139 Different Tumor Entities — A. Menz, J. Zerneke, et al. (2024)
• Expression of Annexin A4 in Cancer: A Tissue Microarray Study Involving More than 17,600 Cancers from 148 Tumor Entities — C. Völkel, N. Malas, et al. (2026)
• Epithelial Cell Adhesion Molecule (EpCAM) Expression in Human Tumors: A Comparison with Pan-Cytokeratin and TROP2 in 14,832 Tumors — A. Menz, N. Lony, et al. (2024)

Browse more research in Acta Oncologica, or return to medical research.