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.
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ABSTRACT: To propose a new algorithm facilitating automated analysis of 1p and 19q status by FISH technique in oligodendroglial tumors with software packages available in the majority of institutions using this technique. We documented all green/red (G/R) probe signal combinations in a retrospective series of 53 oligodendroglial tumors according to literature guidelines (Algorithm 1) and selected only the most significant combinations for a new algorithm (Algorithm 2). This second algorithm was then validated on a prospective internal series of 45 oligodendroglial tumors and on an external series of 36 gliomas. Algorithm 2 utilizes 24 G/R combinations which represent less than 40% of combinations observed with Algorithm 1. The new algorithm excludes some common G/R combinations (1/1, 3/2) and redefines the place of others (defining 1/2 as compatible with normal and 3/3, 4/4 and 5/5 as compatible with imbalanced chromosomal status). The new algorithm uses the combination + ratio method of signal probe analysis to give the best concordance between manual and automated analysis on samples of 100 tumor cells (91% concordance for 1p and 89% concordance for 19q) and full concordance on samples of 200 tumor cells. This highlights the value of automated analysis as a means to identify cases in which a larger number of tumor cells should be studied by manual analysis. Validation of this algorithm on a second series from another institution showed a satisfactory concordance (89%, κ = 0.8). Our algorithm can be easily implemented on all existing FISH analysis software platforms and should facilitate multicentric evaluation and standardization of 1p/19q assessment in gliomas with reduction of the professional and technical time required.PLoS ONE 07/2015; 10(7):e0132125. DOI:10.1371/journal.pone.0132125 · 3.53 Impact Factor
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ABSTRACT: Oligodendroglioma of the spinal cord is a rare tumor that most often presents with spinal cord symptoms. The authors present a case of spinal cord oligodendroglioma that was associated with cerebral rather than spinal cord symptoms. A 30-year-old woman developed nausea, vomiting, and severe headaches. Magnetic resonance imaging of the brain showed meningeal enhancement. The patient underwent a craniotomy with biopsies of the meninges and brain. The biopsy findings revealed an abnormal arachnoid thickening without tumor cells. The patient later developed hydrocephalus and underwent shunt placement. Cerebrospinal fluid cytological findings were negative for tumor cells or infection. She was found to have a cervical cord lesion at C3-4 that was initially nonenhancing but later enhanced after Gd administration. Biopsy of the cord lesion with partial resection showed a WHO Grade II oligodendroglioma with 1p and 19q deletions determined by fluorescence in situ hybridization. Neurooncological treatment with tumor radiation and temozolomide (Temodor) resulted in improvement in radiographic findings, symptoms, and long-term survival. This paper presents an extensive review of the literature, which revealed only 2 other reported cases of cerebral symptoms in adults that preceded spinal cord symptoms in a patient with oligodendroglioma of the spinal cord. It is also the first reported case of oligodendrogliomatosis due to a cervical spinal cord oligodendroglioma with 1p and 19q deletions.Journal of Neurosurgery Spine 07/2009; 10(6):557-63. DOI:10.3171/2009.2.SPINE08853 · 2.36 Impact Factor
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ABSTRACT: Background : Due to overlapping histomorphological features, difference in clinical behavior and treatment response, establishing potential molecular markers to facilitate diagnosis of various genetic subtypes of diffuse gliomas is essential. Aim : To analyze 1p/19q status in diffuse gliomas and correlate it with epidermal growth factor receptor (EGFR) and p53 protein expression. Materials and Methods : 1p/19q status in 43 cases was evaluated by fluorescence in situ hybridization assay. Glial fibrillary acidic protein (GFAP), EGFR and p53 were assessed by immunohistochemistry. Results : Glial fibrillary acidic protein immunopositivity was observed in oligodendrogliomas within minigemistocytes and gliofibrillary oligodendrocytes as perinuclear homogenous blobs. It also highlighted the intermingled reactive astrocytes. Astrocytomas and the astrocytic component of oligoastrocytomas showed a diffuse fibrillary type of staining. 1p and/or 19q loss was seen in 65% (13/20) of oligodendrogliomas and 66.6% (5/9) of mixed oligoastrocytomas. There was one case each of pediatric oligodendroglioma and mixed oligoastrocytoma, none of which showed 1p/19q loss. None of the astrocytomas including two pediatric cases showed this alteration (P < 0.05). p53 was expressed in 57.1% of astrocytomas (8/14), 33% of mixed oligoastrocytomas (3/9) and 10% of oligodendrogliomas (2/20). Majority of oligodendrogliomas (85%; 17/20) and oligodendroglial areas in mixed oligoastrocytomas (77.7%; 7/9) showed a membranous lace-like immunopositivity with EGFR. In contrast, all astrocytomas (Grade II and III) were EGFR negative. Conclusion : Loss of 1p/19q is strongly associated with oligodendroglial phenotype, while astrocytic tumors are more likely to show p53 over-expression. p53 expression and 1p/19q status appear to be mutually exclusive.Neurology India 09/2009; 57(5). DOI:10.4103/0028-3886.57795 · 1.08 Impact Factor