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Loss of DCC Expression and Glioma Progression¹

Departments of Pathology [M. R-M., M. H.], Pediatrics [M. R-M.], Medicine [K. R-C., M. A. R.], and Pharmacology [B. C. E.], Yale School of Medicine, New Haven, Connecticut 06520; Department of Medicine, Veterans Administration Medical Center, West Haven, Connecticut 06516 [M. A. R.]; IARC, 69372 Lyon Cedex, France [H. O., P. K.]; Department of Pathology, Bridgeport Hospital, Bridgeport, Connecticut 06610 [G. K.]; Department of Surgery [A. Y.] and Division of Molecular Medicine and Genetics, Department of Internal Medicine [E. R. F.], University of Michigan Medical Center, Ann Arbor, Michigan 48109

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.

¹ This work was supported in part by a Brain Tumor Society Award (to M. A. R.), NIH Grants CA63297 (to M. A. R.) and CA70097 (to E. R. F.), and Yale Cancer Core Grant CA-16359.

² To whom requests for reprints should be addressed, at Yale School of Medicine, Department of Internal Medicine/Oncology, 333 Cedar Street, P. O. Box 208032, New Haven, CT 06520-8032.

Received 10/16/96. Accepted 12/18/96.

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