Magdalena Hartman

Positron emission tomography 11C‐methionine and survival in patients with low‐grade gliomas

Considerable numbers of patients with low‐grade gliomas experience an early malignant course and may benefit from aggressive treatment. These patients are difficult to identify using established prognostic factors. A retrospective study was performed to determine whether the 11C‐methionine uptake in tumor is a survival factor in adult patients with supratentorial gliomas classified as World Health Organization Grade 2.

Malignant Prolactinoma with Multiple Intracranial Metastases Studied with Positron Emission Tomography

A rare case of a patient with multiple intracranial metastases from a prolactin-secreting pituitary neoplasm is described. At the age of 14 years, the patient had been operated on for a sellar tumor; he presented 12 years later with severe headache, at which time computed tomographic and magnetic resonance imaging scans revealed multiple intracranial metastases. Histopathology examination showed pituitary neoplastic cells with positive immunostaining for prolactin. The patient was investigated with positron emission tomography (PET) and dopamine D2-receptor binding, and the amino acid metabolism of the tumor was characterized in vivo. High dopamine D2-receptor binding and high amino acid metabolism were found in the tumor. The patient was subsequently treated with bromocriptine injections that resulted in a decrease in serum prolactin levels, decreased dopamine D2-receptor binding, reduced amino acid metabolism, and a reduction in tumor volume. This case demonstrates a beneficial effect of bromocriptine treatment in a patient with prolactinoma with multiple intracranial metastases. It also illustrates the great potential of PET in the in vivo characterization of the D2-binding and the high sensitivity of 11C-labeled L-methionine in the follow-up of treatment in patients with pituitary adenomas.

Prognostic value of platelet derived growth factor alpha receptor expression in grade 2 astrocytomas and oligoastrocytomas

Objective: To determine whether the expression of platelet derived growth factor α receptor (PDGFRα) in low grade astrocytomas and oligoastrocytomas is associated with survival. Methods: Formalin fixed and paraffin embedded tumour samples of 40 consecutive patients with supratentorial diffuse astrocytomas and oligoastrocytomas of WHO grade 2, resected between 1986 and 1993, were used for immunohistochemical staining. The fraction of tumour cells expressing PDGFRα protein was quantified and entered into univariate and multivariate survival analyses. Changes in PDGFα expression over time were analysed in seven patients in whom reoperations had been performed. Results: Patients with a relatively high fraction of PDGFRα expressing cells had a more favourable outcome in both univariate (p = 0.04) and multivariate analyses (p = 0.02). Expression of PDGFRα was greater in oligoastrocytomas than in astrocytomas (p = 0.05). In four reoperated patients with histologically confirmed malignant transformation, there was a marked decrease in the number of cells expressing the receptor. Conclusions: There is an association between high PDGFRα expression and long survival time in patients with grade 2 astrocytomas and oligoastrocytomas. The findings suggest that expression of the receptor may be a useful prognostic marker in such patients.

Gene expression analyses of grade II gliomas and identification of rPTPβ/ζ as a candidate oligodendroglioma marker

Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes - astrocytomas, oligodendrogliomas, and oligoastrocytomas - constitute true biological entities is largely unresolved. Furthermore, morphological classification is often ambiguous and would be facilitated by specific subtype markers. In this study, 23 grade II gliomas were expression-profiled and subjected to hierarchical clustering. All six oligodendrogliomas were grouped together in one of two major clusters; a significant correlation was thus observed between gene expression and histopathological subtype. Supervised analyses were performed to identify genes differentiating oligodendrogliomas from other grade II tumors. In a leave-one-out test using 10 features for classification, 20 out of 23 tumors were correctly classified. Among the most differentially expressed genes was rPTPbeta/zeta. The expression of the rPTP beta/zeta protein in oligodendrogliomas and astrocytomas was further validated by immunohistochemistry in an independent set of tumors. All 11 oligodendrogliomas of this set displayed strong staining. In contrast, neoplastic astrocytes were mostly negative for rPTPbeta/zeta staining. In summary, this study demonstrates a correlation between gene expression pattern and histological subtype in grade II gliomas. Furthermore, the results from the immunohistochemical analyses of rPTPbeta/zeta expression should prompt further evaluation of this protein as a novel oligodendroglioma marker.

Horseradish peroxidase histochemistry. A comparison between various methods used for identifying neurons labeled by retrograde axonal transport.

Horseradish (HRP) histochemistry is widely used in neuroanatomical and neuropathological research. In this study the sensitivity of 6 methods commonly used for demonstration of HRP were compared mainly by observation on retrogradely labeled hypoglossal neurons found after injection of HRP into the tongue of adult mice. For this purpose groups of equivalent sections were obtained from the brainstem of each mouse. In one series, 3 diaminobenzidine techniques (Graham-Karnovsky; Malmgren-Olsson; Streit-Reubi), and Mesulams tetramethyl benzidine procedure were compared. In a second series the groups of sections were incubated with DAB (Graham-Karnovsky; Malmgren-Olsson), p-phenylene diamine (Hanker) or TMB (Mesulam; Hardy-Heimer). All the new methods (Streit-Reubi; Malmgren-Olsson; Hanker, Mesulam; Hardy-Heimer) revealed many more labeled neurons per section than the original Graham-Karnovsky technique and Mesulams TMB procedure was in this regard superior to all of the other tested methods. Particularly in sections from the tongue, disturbing precipitates were often obtained with the TMB methods and they are not as well suited as the new DAB procedures for observations on fine details at the light microscopical level. The new DAB methods (Streit-Reubi; Malmgren-Olsson), apart from their high sensitivity, can very well be used for electron microscopy also. Mesulams TMB procedure should therefore be the method of choice in studies on retrogradely labeled neurons if highest possible sensitivity is needed. For studies on fine details in such neurons, i.e. when highest possible resolution is required, any one of the new DAB procedures should be chosen. Due to their lower tendency to form artefactual precipitates, they can be recommended for other HRP applications as well, such as vascular permeability studies, observations on vasogenic edema and perineurial permeability.

Expression of estramustine-binding protein in ependymomas and in human and developing rat ependymal cells

SummaryThe mainstays of primary treatment of ependymoma are aggressive surgery followed by radiotherapy. Although spreading occasionally occurs in the cerebrospinal pathways, chemotherapy is still not established and no ultimate drug has so far been found. Estramustine-phosphate (EMP), with a demonstrated effect on astrocytomain vitro, has been shown to penetrate the blood-tumor barrier and to accumulate in human brain tumor tissue including ependymoma. It has been proposed that the cytotoxic effect of EMP depends on the presence of a binding protein, estramustine-binding protein (EMBP). In the present paper we have, for the first time, immunohistochemically demonstrated an EMBP-like protein in a series of ependymomas. Immunoreactivity was found within the cytoplasm of the tumor cells with a tendency to increase with increasing malignancy of the tumor. In addition, the occurence of EMBP-like protein was demonstrated in human ependymal cells. In the rat brain, a weak immunoreactivity was detected in early fetal neuroepithelial cells while the staining intensity was increased in mature ependymal cells in late fetal, neonatal, and adult rat. Thus, immunoreactivity for an EMBP-like protein was demonstrated in ependymoma tissue, normal human ependyma and in the developing rat ependymal cells.