L1CAM Immunopositivity in Anaplastic Supratentorial Ependymomas: Correlation With Clinical and Histological Parameters

Abstract

Supratentorial ependymomas (ST EPNs) are molecularly characterized, of which the RELA fusion positive tumors are the most common and aggressive subgroup. Moreover, histologically, anaplastic ST EPN (ST-AE) often mimic other central nervous system primary high-grade tumors resulting in a diagnostic dilemma. We aimed to study a cohort of ST-AE; evaluate the expression of two RELA fusion-associated markers-L1CAM and p65 (NF-κB); and correlate their expression with clinical and histological parameters. Cases of ST-AE diagnosed in our department from January 2011 to June 2016 (n = 72) were reviewed. A battery of immunohistochemical markers was employed. A total of 65 confirmed ST-AE were included in the study. Age ranged from 9 months to 60 years. There was a slight predominance in the pediatric population (57%). Male-to-female ratio was 1:1.16. Histomorphological features were varied and mimicked other highgrade tumors in several cases. L1CAM immunopositive tumors constituted 26% of cases and were predominantly seen in young children, in the frontoparietal location, and exhibited clear cell morphology with calcification. A consistent pattern of L1CAM immunopositivity was noted in paired primary and recurrent tumor samples. Our study portrays the varied clinical and histomorphological spectrum of ST-AE. The study emphasizes the association of L1CAM immunopositivity with a wide spectrum of histological parameters, literature on which is scant till date. Since ST EPN-RELA are tumors with aggressive behavior, such a correlation would be clinically relevant, particularly when there is limited access to molecular testing.

Supratentorial Extraventricular Ependymomas: Imaging Features and the Added Value of Apparent Diffusion Coefficient

“…Our study results showed that STEs often occurred in the second to fourth decades of life (mean age 32 years) and both genders were approximately equally affected; these are consistent with previous studies 15,16 . The tumors were most commonly located in the frontal lobe, with the temporal lobe and parietal lobe also frequently affected as reported in previous studies 17,18 . In the present study, the IEs shared similar age and gender characteristics with STEs, but were mostly located in the fourth ventricle, which could easily lead to obstructive hydrocephalus.…”

Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

“…In addition, a ZFTA-RELA fusion was detected in a case primarily diagnosed as centrally located malignant peripheral nerve sheath tumor as well as in a tumor that histologically appeared as 'astroblastoma'. L1CAM, a characteristic histopathological marker for ST-EPN-RELA (23,24), and nuclear p65, the protein encoded by RELA, could be evaluated by immunohistochemistry (IHC) in a limited number of samples from cluster 2, 3 and 4 as well as in ZFTA-RELA-negative and ZFTA-RELA type 8 cases. Apart from one sample in cluster 2, all cases expressed L1CAM to different extents, demonstrating that L1CAM-expression is not restricted to tumors harboring canonical ZFTA-RELA fusions (Fig.…”

Ependymoma Pediatric Brain Tumor Protein Fingerprinting by Integrated Mass Spectrometry Platforms: A Pilot Investigation

“…The most recent molecular studies on ependymomas based on their updated classification are based on immunohistochemistry. Immunohistochemistry studies distinguished supratentorial ependymomas in the RELA-fusion-positive and the yes-associated protein 1 (YAP1)-fusion positive subgroups, the Neural cell adhesion molecule L1 (L1CAM) protein marking the first one and showing the most aggressive behavior [14]. CD44 was instead outlined as a biomarker of prognosis of posterior fossa ependymomas as well as being in association with abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway (PI3K-Akt pathway) [15].…”