Loss of DCC expression and glioma progression.
The deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene on chromosome 18q21, encodes a neural cell adhesion molecule family protein that is most highly expressed in the nervous system. To address the hypothesis that DCC may play a role in glioma development and/or progression, we examined DCC expression by immunohistochemistry in 57 resected human astrocytic tumors. Overall, low-grade astrocytomas were predominantly DCC positive (15 of 16, or 94%), whereas high-grade tumors significantly less often expressed the DCC protein (27 of 41, or 66%; P = 0.03). We were able to directly assess the relationship between DCC expression and tumor progression in 15 patients who initially presented with a low-grade astrocytoma and subsequently recurred with a glioblastoma. Within this panel of paired lesions from the same patient, 14 of 15 (93%) low-grade tumors expressed the DCC protein, whereas only 7 of 15 (47%) corresponding glioblastomas were DCC positive. We also observed that secondary glioblastomas resulting from malignant progression of low-grade astrocytomas were more often DCC negative (8 of 15, or 53%) compared with primary or de novo glioblastomas (6 of 26, or 23%; P = 0.05). These findings implicate DCC inactivation in glioma progression and also demonstrate that DCC expression is preferentially, but not exclusively, lost in the genetic pathway to secondary glioblastoma multiforme.
Reyes-Mugica
M
M
Department of Pathology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Rieger-Christ
K
K
Ohgaki
H
H
Ekstrand
B C
BC
Helie
M
M
Kleinman
G
G
Yahanda
A
A
Fearon
E R
ER
Kleihues
P
P
Reale
M A
MA
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice