Unique Molecular Characteristics of Pediatric Myxopapillary Ependymoma

Abstract

Myxopapillary ependymoma (MEPN) generally can be cured by gross total surgical resection and usually manifest a favorable prognosis. However, surgery is less curative in tumors that are large, multifocal or extend outside the thecal sac. Late recurrences may occur, particularly in pediatric patients. The role of adjuvant therapy is unclear in the clinical management of recurrent tumors. Clinical trial design requires a better understanding of tumor biology. Unique molecular features of MEPN were investigated by using microarray technology to compare the gene expression of five pediatric MEPN to 24 pediatric intracranial ependymoma (EPN). The upregulation of three genes of interest, homeobox B13 (HOXB13), neurofilament, light polypeptide (NEFL) and PDGFRα, was further studied by immunohistochemistry in a larger cohort that included adult MEPN and EPN specimens. Protein expression in MEPN was compared to subependymoma, spinal EPN, intracranial EPN and normal fetal and adult ependyma. Immunoreactivity for HOXB13, NEFL and PDGFRα was strongest in MEPN and virtually absent in subependymoma. Spinal and intracranial EPN generally expressed weak or focal staining. MEPN manifests unique gene and protein expression patterns compared to other EPNs. Aberrant expression of HOXB13 suggests possible recapitulation of developmental pathways in MEPN tumorigenesis. PDGFRα may be a potential therapeutic target in recurrent MEPN.

Genetic expression profiles of adult and pediatric ependymomas: Molecular pathways, prognostic indicators, and therapeutic targets

“…Lukashova-v Zangen and colleagues reported 30 genes that were preferentially expressed in subependymomas (spinal and intracranial) as compared to spinal myxopapillary ependymomas (MEPN), including ETV6, YWHAE, TOP2A, TLR2, ADE2H1, IRAK1, TIA1, TTL, UFD1L, TOMM70A and HSD3B1 [62,67]. MEPN are almost exclusively limited to the distal spinal cord [67].…”

“…MEPN are almost exclusively limited to the distal spinal cord [67]. Korshunov and colleagues found that MEPN expressed high amounts of PLA2G5 (1p36-p34) and ITIH2 (10p15), which distinguished MEPN from intracranial ependymomas [3,29,67].…”

“…MEPN are almost exclusively limited to the distal spinal cord [67]. Korshunov and colleagues found that MEPN expressed high amounts of PLA2G5 (1p36-p34) and ITIH2 (10p15), which distinguished MEPN from intracranial ependymomas [3,29,67]. As compared with intracranial ependymomas, MEPN were also found to overexpress several genes in the HOX family, including HOXB5 (17q21-q22) and HOXB13 [29,34,36,67].…”

“…Korshunov and colleagues found that MEPN expressed high amounts of PLA2G5 (1p36-p34) and ITIH2 (10p15), which distinguished MEPN from intracranial ependymomas [3,29,67]. As compared with intracranial ependymomas, MEPN were also found to overexpress several genes in the HOX family, including HOXB5 (17q21-q22) and HOXB13 [29,34,36,67]. Genes in the HOX family have been the focus of investigation in a variety of other tumors, as they are involved in stem cell renewal, cellular fate determination, and body-segment development [36,[67][68][69][70].…”

“…As compared with intracranial ependymomas, MEPN were also found to overexpress several genes in the HOX family, including HOXB5 (17q21-q22) and HOXB13 [29,34,36,67]. Genes in the HOX family have been the focus of investigation in a variety of other tumors, as they are involved in stem cell renewal, cellular fate determination, and body-segment development [36,[67][68][69][70]. Specifically, HOX groups 10-13 are associated with normal development of the lumbosacral region [67,71].…”