Cytogenetic Analysis of Gemistocytic Cells in Gliomas

Abstract

Abstract. Gemistocytes are glial cells characterized by voluminous, eosinophilic cytoplasm and a peripherally positioned, often flattened nucleus. Gemistocytes, usually present in anoxic-ischemic brains, are regularly encountered in glial neoplasms. The presence of gemistocytes in gliomas has been associated with an unfavorable clinical course, notwithstanding the low proliferative potential of these cells. It is not known whether gemistocytes residing in gliomas are dormant tumor cells, or alternatively, represent interspersed reactive glial cells. Whereas gemistocytic astrocytomas have been subject to various genetic investigations, no genomic analysis comparing individual cells in gliomas has been reported so far. In the present study, 3 astrocytomas, 3 oligodendrogliomas, and 3 mixed oligoastrocytomas, all harboring gemistocytic cells, were genetically analyzed by DNA in situ hybridization to paraffin-embedded, formalin-fixed tissue samples with optimal preservation of cellular morphology. To this end, probes for the centromeric regions of chromosome 7 and 10, known to show copy number aberrations in gliomas, were used. In addition, probes for centromeric regions of chromosomes 1 and 17 were used for the ploidy status of the tumors. The spot counts for the various chromosomes were statistically compared. Gains of chromosome 7 were found in 1 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, and 1 anaplastic oligoastrocytoma. Loss of chromosome 10 was seen in 2 anaplastic astrocytomas, in 1 anaplastic oligodendroglioma, and in 1 anaplastic oligoastrocytoma. In 3 cases, significant differences in spot distributions between gemistocytes and non-gemistocytes were found, but the other cases showed no difference in spot distribution. It is concluded that, although many gemistocytic cells in gliomas may be considered reactive cells, in a subset of tumors, part of the gemistocytic cells should be considered neoplastic.

Established and emerging variants of glioblastoma multiforme: review of morphological and molecular features

“…Furthermore, mutations in p53 have been suggested to exist in tumours of younger patients, tumours with a greater portion of atypical gemistocytes, tumours with significant smaller cell components, and subjects with shorter postoperative survival [80]. Similarly, chromosomal analysis of chromosome 7 and 10 alterations has also been found to be concordant in a subset of GAs suggesting some, but not all, gemistocytic cells to be neoplastic [84]. One study suggesting the presence of small cells better predicted poor prognosis, showed that GA tumour had a mean MIB-1 index of 3.7% (range 0.5-10.5%) primarily restricted to small cell components [5].…”

The Proliferative Activity (Ki-67) and the Level of Vascular Endothelial Growth Factor (Vegf) Gene Expression in Gemistocytic Astrocytomas

“…В литературе можно встретить лишь небольшое количество работ, которые освещают непосред-ственно ГА [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. По сравнению с диффузными астроцитомами GII они характеризуются более агрессивным биологическим поведением, что проявляется более короткой общей выживаемо-стью пациентов (38-49 мес и 69-89 мес.…”

Genetic Diversity of Glioblastoma Multiforme: Impact on Future Therapies

“…Despite of histological overlap clinicopathologic and genetic features are distinct: there are no small cell astrocytomas harboring 1p/19q codeletions, whereas vIII mutant form of EGFR, EGFR amplification and 10q deletions are present in 50%, 69% and 97% of small cell astrocytomas, respectively (Perry et al, 2004). Once thought to represent a reactive component, gemistocytes have been found to harbor TP53 mutations and cytogenetic abnormalities (chromosome 7p gains and 10q losses); therefore, they are now thought to represent a true neoplastic component (Kros et al, 2000).…”