galactocerebroside and Astrocytoma

Astrocytomas are very common intracranial glial cell neoplasms with an inherent tendency to progress. However, the heterogeneity of the morphological features and clinical behavior of the tumors makes accurate prognosis based on the histopathological grading system very difficult. Studies demonstrated that astrocytes have two distinctive cell lineages, and tumors arisen from these two astrocytic lineages have been speculated to have different biological and clinical manifestations. The present study aimed to delineate these two astrocytic lineages in human astrocytomas by using different immunohistochemical markers and to correlate the cell lineages of the tumors with their recurrence. Three markers were used, namely the A2B5 antigen, which is present in type 2 astrocytes but absent in type 1 astrocytes, glial fibrillary acidic protein (GFAP), a marker for astrocytes, and galactocerebroside (GC), a marker for oligodendrocytes. It was found that astrocytomas sharing the A2B5+ lineage (A2B5 positive and GFAP positive) have a significantly higher recurrence rate than the tumors of the A2B5- lineage (A2B5 negative and GFAP positive). Immunohistochemical staining and PCR-single-stranded conformational polymorphism analysis showed that p53 overexpression and p53 mutations were closely associated with the recurrent astrocytomas, and p53 abnormalities were more frequently detected in astrocytomas of the A2B5+ lineage. Quantification of proliferation by counting argyrophil nucleolar organizer regions (AgNORs) indicated a higher AgNOR count in the A2B5+ lineage than the A2B5- lineage. Our findings thus suggest that astrocytomas share similar antigenicity with astrocytes, and that the A2B5+ lineage exhibited a higher recurrence rate than the A2B5- lineage. The higher recurrence rate of the A2B5+ tumors may be in part related to the higher frequency of p53 abnormalities found in the tumors and the higher proliferative activity as reflected by the higher AgNOR count of the tumors.

Topics: Antigens, Neoplasm; Astrocytoma; Brain Neoplasms; Cell Division; Cell Lineage; Galactosylceramides; Gangliosides; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Neoplasm Recurrence, Local; Nucleolus Organizer Region; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Silver; Tumor Suppressor Protein p53

Experimental observations suggest that type 1 and type 2 astrocytes have distinct lineages distinguished, respectively, by the absence or presence of the A2B5 antigen. To investigate the hypothesis that the strikingly different biological behaviors of low-grade and high-grade astrocytomas might be related to cell lineage, 38 astrocytomas (grades I through IV), were examined for the presence of the A2B5 antigen, glial fibrillary acidic protein (GFAP), and galactocerebroside (GC), a marker for oligodendrocytes. Twenty-nine of the tumors (76%) were composed of moderate or high densities of GFAP+ and unlabeled cells, and were devoid of A2B5+ and GC+ neoplastic cells. Only four tumors had high densities (75% to 100%) of A2B5+ cells, three of which were grade I tumors; two tumors, also Grade I, contained moderate densities (20% to 25%) of GC+ cells that had cytologic features of astrocytoma or oligodendroglioma. The findings suggest that most cerebral astrocytomas lack the A2B5 antigen and thus may represent neoplasia along the type 1 astrocyte lineage. In contrast, A2B5+ lineage among astrocytomas, ie, neoplasia with differentiation toward type 2 astrocytes and GC+ oligodendrocytes, is less common and may be correlated with prognostically favorable histopathologic features.

Topics: Adult; Antigens, Neoplasm; Astrocytoma; Brain Neoplasms; Female; Galactosylceramides; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Immunoenzyme Techniques; Male; Middle Aged

Experimental observations provide evidence that galactocerebroside-containing (GC+) oligodendrocytes and glial fibrillary acidic protein-containing (GFAP+) type 2 astrocytes are derived from A2B5+ progenitor cells. Because the cytomorphologic features of oligodendrogliomas resemble those of non-neoplastic oligodendrocytes, it was speculated that neoplastic oligodendroglial cells also have A2B5+ lineage. This hypothesis was investigated by immunostaining histopathologic sections with monoclonal antibodies to GC, A2B5, and GFAP. In 28 tumors, ubiquitous immunolabeling of neoplastic cells with anti-GC and anti-A2B5 was observed. In addition, GFAP+/A2B5+ astrocytes were present in most mixed glial tumors. The findings suggest that oligodendrogliomas, whether or not they contain foci of astrocytoma, are uniformly derived from A2B5+ progenitor cells.

Topics: Antigens, Neoplasm; Astrocytoma; Galactosylceramides; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Oligodendroglioma