Abstract 100: L1CAM(CD171) can be highly expressed in many tumor types but lacks strong associations with tumor phenotype

The cell adhesions molecule L1 (CD171; L1CAM) was initially characterized as an essential protein for neural development but subsequent studies have pinpointed towards a critical role in cancer. Because of its expression in only few normal tissues and its membranous nature L1CAM is a promising drug target. To better comprehend 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. A membranous L1CAM staining was found in 1175 (9.1%) of the 12888 interpretable tumor samples, including 301 (2.3%) with weak, 569 (4.4%) with moderate, and 305 (2.4%) with strong positivity. A total of 73 of 135 tumor entities showed L1CAM expression in at least one case, and 36 tumor categories included at least one case with strong L1CAM staining. The frequency of L1CAM positivity was particularly high in several subtypes of neural and neuroendocrine neoplasms (11.1-100%), endometrium carcinoma (15.4-54.8%), ovarian cancer (22.0-44.6%), cervical adenocarcinoma (27.3%), malignant melanoma (25.3-31.0%), malignant mesothelioma (20.0-29.2%), adenocarcinomas of the gastrointestinal and the biliopancreatic tractus (9.1-18.9%), and in advanced urothelial tumors (13.0-18.2%). In urinary bladder cancer, there was a significant association between L1CAM expression and invasive tumor growth (pTa vs. pT2-4, p<0.0001). In colorectal adenocarcinoma, L1CAM positivity was linked to left-sided tumor location and microsatellite instability. However, L1CAM staining was unrelated to tumor phenotype in muscle-invasive urothelial carcinoma, clear cell and papillary renal cell carcinoma, serous high-grade carcinoma of the ovary, endometrioid endometrium carcinoma, gastric adenocarcinoma, and in pancreatic adenocarcinoma. It is concluded that many different tumor entities could benefit from L1CAM targeting drugs once these should provide sufficiently safe and efficient. However, L1CAM expression does not appear to confer an aggressive phenotype to affected cancer cells. Citation Format: Seyma Büyücek, Magali Lurati, Katharina Möller, Florian Viehweger, Ria Schlichter, Anne Menz, Andreas M Luebke, Viktor Reiswich, Martina Kluth, Elena Bady, Lisa Hornsteiner, 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. L1CAM(CD171) can be highly expressed in many tumor types but lacks strong associations with tumor phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 100.