The CD34 epitope is expressed in neoplastic and malformative lesions associated with chronic, focal epilepsies

Abstract

The etiology and pathogenesis of complex focal lesions associated with chronic, intractable epilepsy are largely unknown. Some data indicate that malformative changes of the central nervous system may precede the development of gangliogliomas and other epilepsy-associated neoplasms. In the present immunhistochemical study, we have examined epilepsy-associated lesions for CD34, a stem cell marker transiently expressed during early neurulation. Surprisingly, most tissue samples from patients with chronic epilepsy (n = 262) revealed neural cells immunoreactive for CD34. Prominent immunoreactivity was detected in gangliogliomas (74%), low-grade astrocytomas (62%) and oligodendrogliomas (59%). Only 52% of non-neoplastic, malformative pathologies, such as glio-neuronal hamartias or hamartomas showed solitary or small clusters of CD34-immunoreactive cells. None of the adult control tissues (n = 22), none of the specimens obtained from the developing human brain (n = 44) and none of those tumor samples from patients without epilepsy (n = 63) contained CD34-immunoreactive neural cells. However, a malignant teratoma with microscopic features of early neural differentiation displayed a focal CD34-immunoreactive staining pattern. The majority of CD34-immunoreactive cells co-localized with S-100 protein and a small subpopulation was also immunoreactive for neuronal antigens. CD34 may, thus, represent a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathological changes in epilepsy patients. The CD34 immunoreactivity of these lesions indicates an origin from dysplastic or atypically differentiated neural precursors. Further studies may elucidate the functional significance of CD34 expression during the pathogenesis of epilepsy-related focal lesions as well as during neurogenesis.

In situ-RT and immunolaser microdissection for mRNA analysis of individual cells isolated from epilepsy-associated glioneuronal tumors

“…Considering the role of CD34 as stem cell epitope, these findings support the hypothesis that gangliogliomas contain neural elements with compromised or atypical differentiation. 12 …”

“…Intriguingly, gangliogliomas express the stem cell epitope CD34, 12 suggesting an origin from a developmentally compromised precursor lesion. However, the cellular identity of CD34 expressing elements remains enigmatic.…”

“…However, the cellular identity of CD34 expressing elements remains enigmatic. 12 However, CD34 expression has been also described in activated microglia, 13,14 cellular elements frequently observed in brain tissue following epileptic attacks. In order to characterize the cellular origin of CD34-expressing cells in gangliogliomas, we employed in situ-RT primers specific for three neural lineage markers: glial fibrillary acidic protein (GFAP), neurofilament (NFM) and myelin basic protein (MBP); as well as human leukocyte antigen (HLA-DQ) and CD34.…”

Neuronal and Mixed Neuronal-Glial Tumors of the Central Nervous System

“…Neuronal protein markers, such as synaptophysin, neurofilaments, MAP2, and Neu N, are used to reveal the neuronal component in gangliogliomas.. However, use of the onco-fetal CD34 antigen can be positive, as CD34 is absent in neural cells of the adult brain but consistently expressed in 70% to 80% of gangliogliomas, especially those arising from the temporal lobe (15). Staining for GFAP reveals the astrocytic component the neoplastic glial element of gangliogliomas.…”

Tumor-associated epilepsy

“…5,8,22,28 These lesions contain both a highly differentiated glial component and also a dysplastic neuronal component. Gangliogliomas are the most frequent tumor in patients with focal epilepsy.…”