Acta oncologica (Stockholm, Sweden) · 2025
L1CAM/CD171 expression in human tumors and its association with tumor phenotype.
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Büyücek Seyma, Lurati Magalie, Möller Katharina, Fiehweger Florian, Schlichter Ria, Menz Anne, Luebke Andreas M, Reiswich Viktor, Kluth Martina, Hube-Magg Claudia, Hinsch Andrea, Lutz Florian, Weidemann Sören, Jacobsen Frank, Dum David, Bernreuther Christian, Lebok Patrick, Sauter Guido, Marx Andreas H, Simon Ronald, Fraune Christoph, Gorbokon Natalia, Burandt Eike, Minner Sarah, Steurer Stefan, Clauditz Till S, Krech Till, Chirico Viktoria, Lennartz Maximilian
Аннотация
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.
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.