Abstract
The latest WHO guideline of CNS tumor defined a RELA fusion-positive ependymoma type with extremely poor prognosis, and the expression of L1CAM was correlated well with the presence of RELA fusion. However, the L1CAM protein expression in large sample gliomas other than ependymoma, its relationship with the RELA gene and its prognostic significance remained unknown. We examined the expression of L1CAM in 565 glioma cases (WHO grade I-IV). The L1CAM IHC-positive cases were selected to test RELA fusion with FISH break-apart probes. L1CAM was positive in 109 cases (19.29%) of all 565 glioma cases, with 18.27% in low-grade gliomas and 19.84% in high-grade gliomas, respectively. Unlike ependymoma, L1CAM protein expression was not correlated with the C11orf95-RELA fusion gene in other gliomas, but it had correction with the patient age (older than 45-year-old, p = 0.006), ATRX mutation (p = 0.003) and Ki67 (p = 0.007). High expression of L1CAM was an independent prognostic factor in our cohort. Further analysis demonstrated that L1CAM strong positive expression was significantly associated with poor prognosis in gliomas, both in our cohort (p < 0.001) and TCGA (p < 0.009) dataset. Although uncorrelated with C11orf95-RELA fusion, L1CAM was a significant poor prognostic marker in glioma patients. More aggressive treatment should be taken for these patients and L1CAM might be a promising therapeutic target in glioma.
Highlights
Glioma is the most common malignant and highly aggressive brain tumor, possessing the characteristics of infiltrating growth and easy recurrence
L1CAM was defined as highly positive cases when strong cytoplasmic and membranous staining expressed in tumor cells, and vascular endothelial cells were an internal negative control (Figures 1(a)–1(d))
High expression of L1CAM was correlated with patient age (p = 0:006), ATRX status (p = 0:003), and Ki-67 index (p = 0:007), but no correlation was found between L1CAM and gender, tumor location, WHO grade, IDH status, and P53 status (Table 1)
Summary
Glioma is the most common malignant and highly aggressive brain tumor, possessing the characteristics of infiltrating growth and easy recurrence. Glioblastoma (GBM) is one of the most lethal and aggressive brain tumors with extremely poor prognosis and high rates of recurrence. In the past few years, a lot of studies discussed the function and expression of L1CAM in human malignancies of different patient samples. It was a predictive factor of poor prognosis with vulvar cancer, endometrial cancer, gastric cancer, etc. Only few studies researched L1CAM in glioma, it found to act as a putative role in the histogenesis of glioma, which conferred chemoresistance and stimulated glioma cell motility and proliferation [2,3,4]
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