Abstract
Background: Malignant gliomas are heterogeneous, diffuse and invasive by nature. Histopathological identification of glioma tumor cells is mandatory to characterize the tumors and the extent of infiltration in the surrounding normal parenchyma. Methods: In order to identify specific markers for tumor cells not expressed in non-neoplastic brain tissues, we used a well-annotated tissue microarray (TMA) containing 45 samples from patients that suffered from several subtypes of low grade and high grade gliomas (pilocytic astrocytoma, oligoastrocytoma, low grade astrocytoma, anaplastic astrocytoma, primary and secondary glioblastomas), non-glial tumors (medulloblastoma and metastasis) as well as fetal, epileptic, and gliotic specimens used as non-tumoral control tissues. The TMA was assessed for 24 proteins involved in tumor proliferation, migration, invasion, and differentiation, or acting as transcription factors and metabolic enzymes. Results: This immunohistological analysis revealed that nestin and secreted protein, acidic and rich in cysteine (SPARC) are expressed in tumor cells in all glioma subtypes and developmental tissues but rarely in mature epileptic tissue. In addition to these two markers, the expression of mutated isocitrate dehydrogenase 1 (IDH1(R132H)) also identified tumor cells but only in some subtypes of gliomas. Conclusions: Taken together, our data suggest that the combination of nestin and SPARC expression characterizes tumor glioma cells. These proteins may represent relevant glioma immunohistological markers that might be molecular targets in glioma therapy.
Highlights
Gliomas are a heterogeneous group of neuroectodermal tumors that arise from the glia
Taken together, our data suggest that the combination of nestin and SPARC expression characterizes tumor glioma cells
Some tumors were represented by 5 samples forming an invasion gradient (3 Low-grade astrocytoma (LGA), 3 OA, 3 pilocytic astrocytoma (PiA), 3 AA, 8 primary glioblastoma multiforme (GBM) (pGBM), 3 secondary GBM (sGBM), 2 Med), each separated by 2-4 mm from the center to the periphery of the tumor, in order to visualize potentially infiltrative tumor cells into the surrounding normal appearing brain parenchyma
Summary
Gliomas are a heterogeneous group of neuroectodermal tumors that arise from the glia. Despite the huge technical development of diagnostic and surgical procedures, the prognosis for patients with gliomas, and glioblastoma multiforme (GBM), remains poor. The survival of these patients does not exceed more than few months (11 to 16 months) after surgical resection and supplemental treatments including chemotherapy and radiation therapy [1,2]. 30% of radiologically suspected low-grade gliomas are histopathologically classified as malignant gliomas Such discrepancies between radiological and histopathological diagnosis indicate that imaging alone is not sufficient in predicting the status of brain tumors. A histopathological approach is mandatory in any case of suspected glioma to provide diagnosis, prognosis and prediction of treatment for brain tumors. Histopathological identification of glioma tumor cells is mandatory to characterize the tumors and the extent of infiltration in the surrounding normal parenchyma
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