Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas

Abstract

Ependymomas are glial neoplasms occurring in any location throughout the central nervous system and supposedly are derived from radial glia cells. Recent data suggest that these tumors may have different biological and clinical behaviors according to their location. Pediatric supratentorial and infratentorial ependymoma (SE and IE) were compared with respect to clinical and radiological parameters and immunohistochemistry (IHC). Neuronal markers were specifically assessed by IHC and quantitative PCR (qPCR). No single morphological or radiological characteristic was associated with location or any neuronal marker. However, there was a significant overexpression of neuronal markers in SE compared with IE: neurofilament light polypeptide 70 (NEFL)-positive tumor cells were found in 23 of 34 SE and in only 4 of 32 IE (P < .001). Among SE, 10 of 34 exhibited high expression of NEFL, defined as more than 5% positive cells. qPCR confirmed the upregulation of neuronal markers (NEFL, LHX2, FOXG1, TLX1, and NPTXR) in SE compared with IE. In addition, strong NEFL expression in SE was correlated with better progression-free survival (P = .007). Our results support the distinction of SE and IE. SEs are characterized by neuronal differentiation, which seems to be associated with better prognosis.

Fig. 1.

Histological variants and IHC findings in SE: (A) classic ependymoma histology; (B) clear cell ependymoma; (C) papillary ependymoma; (D) tanicytic ependymoma; (E) GFAP immunostaining showing a classical perivascular enhancement; and (F) EMA staining, with positivity in dots, some cases showing an apical cell-membrane staining in true rosettes (insert). Original magnifications: ×200 (A, B, and E), ×100 (C), and ×400 (F).

Fig. 2.

The Kaplan–Meier survival curves in SE according to surgical treatment. (A) OS and (B) PFS.

Fig. 3.

Immunostaining for neuronal markers in SE. (A and B) High expression of neurofilament light polypeptide (NEFL) defined as more than 5% positive tumor cells, which often showed elongated morphology. (C) Cellular detail of NEFL staining, including a positive cell in mitosis and strong cytoplasmic pattern. (D) Immunostaining for neuronal nuclei (NEUN). (E) Immunostaining for synaptophysin. (F) Immunostaining for chromogranin A. Original magnifications: ×200 (A), ×400 (B), ×600 (C–F).

Fig. 4.

PFS in months for SE, according to neurofilament light polypeptide (NEFL) immunostaining—strong vs weak/no staining.

Fig. 5.

qPCR confirms the overexpression of neuronal markers in SE (supra, n = 10) when compared with IE (infra, n = 11). (A) NEFL. (B) Lim homeobox protein 2 (LHX2). (C) Forkhead box G1B (FOXG1). (D) T-cell leukemia homeobox 1 (TXL1). (E) Neuronal pentraxin receptor (NPTXR). (F) Reelin (RLN). (G) Tenascin C (TNC). (H) NOTCH1. Normal brain was used as a reference.