An association of molecular genetic parameters in gliomas and meningiomas with histological type and grade

Introduction:  Primary brain tumors account for about 2% of all adult malignancies. The incidence of primary brain tumors has nearby doubled within the past 30 years and was 7.95 per 100 000 inhabitants in the Czech Republic (in 2010). The most common brain tumors are gliomas and meningiomas. Gold standard for the classification of primary brain tumors is WHO classification; however, this classification is based on subjective criteria. Thus the individual prognosis and prediction of response to treatment remains still inadequate. Within the past 20 years, the number of biomarkers (chromosomal, genetic and epigenetic alterations, associated with a specific histological type and grading) has been identified in gliomas. Typical chromosomal aberrations associated with histological subtypes and grading were revealed in meningiomas too.

Material and Methods:   To detect the most frequent chromosomal aberrations in fresh frozen or FFPE tumor samples, the method of interphase fluorescence in situ hybridization (i-FISH), including directly labelled, locusspecific and/or centromeric probes made by Abbott (Vysis), or Kreatech (Poseidon) were used. Histological type and grade of brain tumor samples were determined according to WHO criteria of tumor classification by analysing hematoxylin-eosin stained slides and immunohistochemically stained slides of processed tumor tissues.

Results: Since 11/2007 till 12/2012, 436 brain tumor samples were collected. 312 (72%) cases were diagnosed with primary brain tumor and these samples were analysed by i-FISH. 111 (25%) cases of the tumors were metastatic tumors of various organ origin (not analysed). i-FISH was unsuccessful in 13 cases (3% of samples). Gliomas accounted for 63% of cases, meningiomas accounted for 30% of analysed samples. Neurinomas, medulloblastomas, papi llomas and primitive neuroectodermal tumors accounterd for remaining 7% of collected brain tumor samples. Genetic aberrations associated with high grade gliomas were found in 38% of patologically diagnosed cases of low grade gliomas (gr. I and II ). Aberrations associated with diagnose of atypical or anaplastic meningioma were found in 47% of cases of pathologically diagnosed meningiomas gr. I. The relapse occurred in 8.5% of cases with benign meningiomas gr. I.

Conclusions: Chromosomal aberrations found in patients with primary brain tumors by i-FISH contributed to accuracy improvement of the histopathological diagnosis. Aberrations with aggressive biological potential can indicate a higher risk of progression or recurrence of the tumor. In these cases careful monitoring by imaging methods was performed, especially when radical extirpation of the tumor was impossible.