Assessment of 1p/1.9q deletions by fluorescence in situ hybridization in gliomas
ABSTRACT This study assessed the efficacy of FISH for detecting 1p/19q deletion in gliomas on 77 paraffin-embedded tissue samples, of which 42 cases (55%) were positive for 1p/19q codeletion; 7 of the 42 had a previous history of glioma. In one case, analysis failed. The remaining 34 cases were negative; of these, three had a previous history of glioma and one had the reverse 1q/19p deletion. A majority of the 10 recurrent gliomas had progressed, and 70% had a 1p/19q deletion. The signal pattern in a majority of 1p/19q codeletion cases was a single red marker signal and two green reference signals (1R2G) for both probe sets. One case had a different signal pattern for chromosomes 1 and 19 (1R2G and 2R4G), as seen in polysomy cells. Three cases had two target and four control signals (2R4G), as seen in tetraploid cells. Eleven had complex signal patterns seen in diploid and polyploid cells (1R2G/<nRnG). A majority of these complex cases (8 of 11, or 73%) had high-grade oligodendroglioma (n = 4) or oligoastrocytoma (n = 4). The frequency of 1p/19q combined deletion in oligodendroglioma (n = 40), oligoastrocytoma (n = 21), and astrocytoma (n = 8) was 65, 60, and 25%, respectively. Elucidated in this paper are the various FISH signal patterns observed in gliomas and a need for a uniform nomenclature for improved diagnosis.
SourceAvailable from: Paola Cassoni[Show abstract] [Hide abstract]
ABSTRACT: Evaluation of the molecular status of 1p and 19q is a major relevant diagnostic, prognostic, and predictive tool for oligodendroglial brain tumors. Fluorescence in situ hybridization (FISH) is the most commonly used technique for determining 1p and 19q allelic losses, but it lacks fully standardized criteria for analysis. This lack of standardization has led to interinstitutional disagreement in the interpretation of results, thereby contributing to a "gray prognostic zone" that includes codeleted patients with an unexpectedly unfavorable outcome. To optimize the prognostic potential of 1p/19q status determination, we first compared the actual criteria used for FISH reading (i.e. different ratio cutoff values and the percentage of neoplastic nuclei carrying this chromosomal deletion) in a retrospective series of 143 pure and mixed oligodendroglial tumors. We then created a "weighted" FISH reading based on the merged ratio and percentage of neoplastic cells carrying the deletion that was further differentially modulated for 1p and 19q, respectively. This weighted codeletion setting significantly strengthened the favorable prognostic power of 1p/19q losses by reducing the number of poor outcomes from 42% to 12.5% for patients with codeleted tumors. Thus, by identifying as codeleted only those cases with more than 50% of cells having a combined loss of 1p (using 0.7 ratio cutoff) and 19q (using 0.8 ratio cutoff) arms, we created a molecular report that bears higher clinical impact and strengthens the prognostic potential of 1p/19q allelic loss.04/2013; 72(5). DOI:10.1097/NEN.0b013e3182901f41
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ABSTRACT: To develop a new ImmunoFISH technique for the study of oligodendrogliomas by combining a standard immunohistochemical stain using MIB-1 antibody with a standard FISH technique using commercial 1p36 and 19q13 chromosomal probes.PLoS ONE 06/2014; 9(6):e100342. DOI:10.1371/journal.pone.0100342 · 3.53 Impact Factor
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ABSTRACT: Few studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N = 16 probes) interphase—FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed ≥2 tumor cell clones, with higher numbers among high- versus low-grade gliomas (p = 0.001). Nine different cytogenetic patterns were found in the ancestral tumor clones. In most gliomas, ancestral clones showed abnormalities of chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition of additional abnormalities followed by tetraploidization. Conversely, early tetraploidization was associated with low-grade astrocytomas—2/3 pilocytic and 3/6 grade II diffuse astrocytomas—and combined loss of 1p36/19q13 with oligodendrogliomas, respectively; both aberrations were associated with a better patient outcome (p = 0.03). Overall, our results support the existence of different pathways of intratumoral evolution in gliomas KeywordsGlioma-Intratumoral heterogeneity-Clonal evolution-CytogeneticsNeurogenetics 05/2010; 11(2):227-239. DOI:10.1007/s10048-009-0217-x · 2.66 Impact Factor