title: Loss of DCC expression and glioma progression.
abstract: 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.
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: M
authors.initials: M
authors.lastname: Reyes-Mugica
authors.forename: K
authors.initials: K
authors.lastname: Rieger-Christ
authors.forename: H
authors.initials: H
authors.lastname: Ohgaki
authors.forename: B C
authors.initials: BC
authors.lastname: Ekstrand
authors.forename: M
authors.initials: M
authors.lastname: Helie
authors.forename: G
authors.initials: G
authors.lastname: Kleinman
authors.forename: A
authors.initials: A
authors.lastname: Yahanda
authors.forename: E R
authors.initials: ER
authors.lastname: Fearon
authors.forename: P
authors.initials: P
authors.lastname: Kleihues
authors.forename: M A
authors.initials: MA
authors.lastname: Reale
mesh_terms: 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