LOSS OF DCC EXPRESSION AND GLIOMA PROGRESSION

The deleted in colorectal cancer (DCC) gene, a candidate tumor suppres sor gene on chromosome 18q21, encodes a neural cell adhesion mol ecule family protein that is most highly expressed in the nervous system. T o address the hypothesis that DCC may play a role in glioma developmen t and/or progression, we examined DCC expression by immunohistochemist ry in 57 resected human astrocytic tumors, Overall, low-grade astrocyt omas 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 relationsh ip between DCC expression and tumor progression in 15 patients who ini tially presented with a low-grade astrocytoma and subsequently recurre d with a glioblastoma. Within this panel of paired lesions from the sa me patient, 14 of 15 (93%) low-grade tumors expressed the DCC protein, whereas only 7 of 15 (47%) corresponding glioblastomas were DCC posit ive, We also observed that secondary glioblastomas resulting from mali gnant progression of low-grade astrocytomas mere more often DCC negati ve (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 i n glioma progression and also demonstrate that DCC expression is prefe rentially, but not exclusively, lost in the genetic pathway to seconda ry glioblastoma multiforme.