Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization

Wessels, Peter H; Hopman, Anton H. N.; Ummelen, Monique; Krijne-Kubat, B.; Ramaekers, F.C.S.; Twijnstra, A.

doi:10.1212/wnl.56.9.1224

Cited by 12 publications

(5 citation statements)

References 8 publications

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“…So far, no single immunohistochemical marker can clearly distinguish these cases. In recent years, attempts to discriminate between reactive and neoplastic astrocytes have employed various molecular genetic methods, including in situ hybridization to detect chromosomal aberrations absent in non‐neoplastic tissue (50). However, these methods are elaborate, expensive and cannot replace the usefulness of immunostaining.…”

Section: Discussionmentioning

confidence: 99%

WT1 Expression Distinguishes Astrocytic Tumor Cells from Normal and Reactive Astrocytes

et al. 2008

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Particularly in small brain biopsies, it might be difficult to distinguish reactive astrogliosis from low-grade or infiltration zones of high-grade astrocytomas. So far no immunohistochemical marker allows a reliable distinction. Recently, the over-expression of Wilms' tumor gene product WT1 was reported in astrocytic tumor cells. However, no sufficient data on WT1 expression in normal or reactive astrocytes are available. Therefore, we investigated WT1 expression in paraffin-embedded brain sections from 28 controls, 48 cases with astrogliosis of various etiology and 219 astrocytomas [World Health Organization (WHO) grades I-IV] by immunohistochemistry. In normal brains and in astrogliosis, expression of WT1 was restricted to endothelial cells. In astrocytomas, WT1-positive tumor cells were found in pilocytic astrocytomas (66.7% of cases), diffuse astrocytomas (52.7%) WHO grade II (52.7%), anaplastic astrocytomas (83.4%) and glioblastomas (98.1%). Overall, the majority of all astrocytic neoplasms (84.5%) expressed WT1. Establishing a cut-off value of 0% immunoreactive tumor cells served to recognize neoplastic astrocytes with 100% specificity and 68% sensitivity and was associated with positive and negative predictive values of 1 and 0.68, respectively. Therefore, WT1 expression in astrocytes indicates a neoplastic origin and might represent an important diagnostic tool to differentiate reactive from neoplastic astrocytes by immunohistochemistry.

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Section: Discussionmentioning

confidence: 99%

WT1 Expression Distinguishes Astrocytic Tumor Cells from Normal and Reactive Astrocytes

et al. 2008

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“…Overall survival was assessed from the patients' records. As controls, 10 samples with non‐neoplastic reactive gliosis were examined (Wessels et al, 2001). These samples were derived at postmortem examination from patients who died from non‐neoplastic neurological causes, that is, brain infarction (n = 5), hemorrhagic infarction (n = 1), traumatic hemorrhage (n = 2), and hypoxic encephalopathy (n = 2).…”

Section: Methodsmentioning

confidence: 99%

Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2

Wessels

Twijnstra

Kessels

et al. 2001

Genes Chromosomes & Cancer

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The clinical course of astrocytoma grade 2 (A2) is highly variable and is not reflected by morphological characteristics. Earlier studies using small series of A2 cases suggest that in situ hybridization (ISH) with chromosome-specific DNA probes allows for frequent detection of aneusomy 1, trisomy 7, and monosomy 10. The role of trisomy 7 in astrocytoma carcinogenesis is disputed, however, because of its presence in non-neoplastic brain tissue, as detected by karyotyping. Our objective was to investigate whether there was a correlation between chromosomal aberrations and survival in a series of 47 cases of A2. All cases were evaluated for numerical aberrations of chromosomes 1, 7, and 10 by ISH. Chromosomal aberrations were detected in 68% of cases of A2. Trisomy/polysomy 7 was seen in 31 cases (66%), 22 of which (47%) had a high percentage of this numerical aberration. Only 11 of these 22 cases also showed aneusomy for 1 or 10. No cells or only a few cells with aberrations were detected in non-neoplastic control samples. Using Kaplan-Meier analysis, trisomy/polysomy 7 correlated significantly with shorter survival. Hence, as determined by ISH, trisomy/polysomy 7 is absent in non-neoplastic brain tissue and is frequently detected in A2, correlating with the malignant progression of the disease.

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“…Several techniques besides histology have been applied to distinguish gliomas from gliosis: microsatellite analysis to examine loss of heterozygosity (17), fluorescent in situ hybridization (FiSH) (42), in situ hybridization (43), comparative genomic hybridization (44,45), rna microarray expression analysis (46), certain proteomic techniques (47) and microdissection techniques, coupled with polymerase chain reaction amplification (48).…”

Section: Discussionmentioning

confidence: 99%

Tissue array analysis for the differentiation of gliosis from gliomas

et al. 2011

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Abstract. The aim of this study was to provide a methodology to make a clear distinction between malignant tumors and morphologically similar benign processes, by examining the expression of eGFr, VeGF, HiF1-α, survivin, Bcl-2 and p53 proteins. Four groups of patient samples were studied: group 1, low-grade astrocytomas (WHo grades i-ii) (n=6); group 2, peripheral area of high-grade astrocytomas (WHo grades iii-iV) (n=5); group 3, gliomatosis cerebri (n=11); and group 4, reactive gliosis (n=6). Tissue arrays (Tas) were designed to study apoptosis, angiogenesis and invasion-related proteins by immunohistochemistry (iHc). By means of nonparametric analysis (Mann-Whitney u test), eGFr staining was shown to be significantly lower in reactive gliosis than in the low-and high-grade astrocytomas (p=0.015 and p=0.030, respectively); Bcl-2 immunoreactivity was significantly higher in the gliomatosis cerebri samples than in the reactive processes (p=0.005); and finally, Bcl-2 presented significantly lower expression levels in reactive gliosis compared to the peripheral areas of high-grade astrocytomas (p=0.004). The results indicate that Bcl-2 and eGFr may be useful in conducting differential diagnosis between the above groups, while the expression of the remaining antibodies does not appear to aid in distinguishing between the samples analyzed.

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Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization

Cited by 12 publications

References 8 publications

WT1 Expression Distinguishes Astrocytic Tumor Cells from Normal and Reactive Astrocytes

WT1 Expression Distinguishes Astrocytic Tumor Cells from Normal and Reactive Astrocytes

Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2

Tissue array analysis for the differentiation of gliosis from gliomas

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