Molecular genetic changes in low grade glioma – case report

Introduction: Gliomas are the most common primary brain tumors. Despite the important advantages in the knowledge of molecular abnormalities related to its biological behavior and new treatment options, the prognosis of gliomas, especially high grade gliomas, has not improved in the last years.

The most common and aggressive type of primary brain tumor is glioblastoma multiforme (GBM). It is known that GBMs develop by two different genetic pathways. The pathway including TP53 inactivation is characteristic for secondary GBM arising in younger adults from preexisting, less malignant lesion (low grade gliomas, LGG), whereas pathway with EGFR amplification most commonly occurs in older patients with primary glioblastoma.

Aim: In our work we want to discuss the case of patient with histologically diagnosed astrocytoma grade II (LGG).

Material and methods: Native sample of tumor and the FFPE sections of the same tumor sample of thirty years old man were examined. Type of tumor was defined by pathologist as fibrillary astrocytoma gr. II. To detect status of chromosomes 7, 9, 10, 12, 13, 17, status of genes EGFR, CDKN2A (p16), PTEN, MDM2, RB1, TP53 and to confirm diagnosis of astrocytoma gr. II, interphase FISH was performed.

Results: Genetic abnormalities associated with low grade gliomas were detected in small proportion of native tumor cells: polysomy of chromosome 7, monosomy of chromosome 17. However, in other proportion of cells, deletion of tumor suppressor genes CDKN2A, PTEN, monosomy of chromosome 10, 13 and amplification of EGFR and MDM2 genes were found. These aberrations are associated with high grade gliomas (HGG), especially with primary GBM. With respect to histopathological diagnosis these findings were confirmed by iFISH on FFPE sections using EGFR/CEP7 probe. Amplification of EGFR was found in isolated tumor cells.

Conclusions: The isolated cells with aggressive biological potential were found in the background of low grade cells in the sample with histopathological diagnosis of fibrillary astrocytoma. It is not clear what cells will prevail in the whole tumor. Young age of the patient and small proportion of aberrant cells give evidence for diagnosis of LGG. On the contrary, short clinical history of patient and type of found molecular genetic abnormalities give evidence for diagnosis of HGG. Because of contradictory conclusions of histopathological and molecular genetic methods it is difficult to predict patient´s prognosis.