Highly migratory neuroectodermal cells share a common embryonic origin with cells of the central nervous system (CNS). They include enteric, parasympathetic, sympathoadrenal, and sensory neurons of the peripheral nervous system, Schwann cells, melanocytes, endocrine cells, and cells forming connective tissue of the face and neck. Because of their common embryologic origin, these cells and the
tumors that derive from them can share genetic and antigenic phenotypes with
gliomas,
tumors derived from CNS glia. We recently discovered that
chlorotoxin (ClTx), a 4-kD
peptide purified from Leiurus quinquestriatus scorpion, is a highly specific marker for
glioma cells in biopsy tissues (Soroceanu et al.
Cancer Res 58:4871-4879, 1998) that can target
tumors in animal models. We report on the specificity of ClTx as a marker for
tumors of neuroectodermal origin that include
peripheral neuroectodermal tumors (
PNET) and
gliomas. Specifically, we histochemically stained frozen and
paraffin tissue sections of human biopsy tissues from 262 patients with a synthetically manufactured and biologically active ClTx bearing an N-terminal
biotin. The vast majority (74 of 79) of primary human
brain tumors investigated showed abundant binding of ClTx with greater than 90% ClTx-positive cells in each section. By comparison, 32 biopsies of uninvolved brain used for comparison were largely ClTx-negative, with only a few isolated reactive astrocytes showing some ClTx binding. However, as with
gliomas, the vast majority of
PNETs examined showed specific ClTx binding (31 of 34). These include
medulloblastomas (4 of 4),
neuroblastomas (6 of 7),
ganglioneuromas (4 of 4),
melanomas (7 of 7), adrenal
pheochromocytomas (5 of 6), primitive
PNET (1),
small cell lung carcinoma (2 of 3), and
Ewing's sarcoma (2 of 2). Under identical staining conditions, normal tissues from brain, skin, kidney, and lung were consistently negative for ClTx. These results suggest that
chlorotoxin is a reliable and specific histopathological marker for
tumors of neuroectodermal origin and that
chlorotoxin derivatives with cytolytic activity may have therapeutic potential for these
cancers.