Analysis of P⁷⁸: A Novel Cytoplasmic Membrane-Associated Protein Encoded on Chromosome 19q13.3 in Glioma Specimens

Allelic losses of the q13.3 region of chromosome 19 have been documented in all major types of diffuse gliomas, strongly suggesting the presence of a 19q13.3 tumor suppressor gene responsible for these malignancies. The P⁷⁸ gene precisely maps to 19q13.3, the glioma candidate region, and encodes a recently identified novel protein (P⁷⁸). The purpose of this study was to determine P⁷⁸ protein expression in gliomas. Serial analysis of gene expression (SAGE) reveals P⁷⁸ mRNA expression to be significantly reduced in high-grade gliomas such as glioblastoma (GB), as compared with the low-grade tumors including astrocytomas, oligodendrogliomas, and ependymomas. We observed the distribution of staining of P⁷⁸ protein was concentrated on the cell membranes of the luminal epithelial cells, not cytoplasm. In contrast, the pre-immune serum controls demonstrated no staining. These results demonstrate that P⁷⁸ protein is highly expressed in the cytoplasmic membranes of low but not high-grade astrocytomas, and correlates with grade of malignancy. In these double immunostaining experiments, the anti-Map-2 and anti-NeuN antibodies did not stain round cells that were stained with the anti-P⁷⁸ carboxyl-terminal peptide antibodies, demonstrating that these round cells were not neurons, and likely protoplasmic astrocytes. Current results also suggest that the astrocytes stained with the anti-P⁷⁸ carboxyl-terminal peptide antibody are likely protoplasmic astrocytes. We also observed preincubation of anti-P⁷⁸ carboxyl-terminal antibodies with immunizing peptides abolished immunostaining in gliomas. These results suggest a role for the P⁷⁸ protein in the process of abnormal growth in glial tumors.