Increased Human Polo-Like Kinase-1 Expression in Gliomas

PLK-1 (polo-like kinase) belongs to the family of serine/threonine kinases and is involved in spindle formation, centrosome cycles and chromosome segregation. Hence, the kinase is tightly linked to cell proliferation. We could detect immunohistochemically highly expressed PLK protein in astrocytic tumours depending on the grade of anaplasia, in commercially available human glioma cell lines (U87MG, U118MG, U138MG), in one immortalized cell culture derived from a glioblastoma patient and in a primary culture derived from a glioblastoma patient. The highest labelling of PLK-1 was demonstrated in glioblastomas. There was a significant correlation between the PLK expression and the nuclear immunoreactivity of MIB-1. PLK-mRNA, found in all tumour specimens investigated emphasizes the close correlation to proliferation and growth. Furthermore, the relation of the PLK-1 expression to the Mitogen-activated Protein Kinase Cascades was studied by applying various highly specific inhibitors. While all inhibitors minimized the cell density, only the PLC inhibitor clearly lead to a reduced PLK-1 expression in the three cell lines U87MG, U118MG, U138MG.     

Gliomatosis Cerebri: Post-mortem Molecular and Immunohistochemical Analyses in a Case Treated with Thalidomide

Gliomatosis cerebri (GC) is a rare tumor of the central nervous system (CNS) characterized by widespread diffuse infiltration of the brain and spinal cord by neoplastic glial cells. We report the case of a 17-year-old boy with a bioptically diagnosed fibrillary astrocytoma. The administration of thalidomide, which was suggested to be beneficial in the treatment of human cancers, had no substantial clinical effect on our patient. Autopsy studies revealed a diffuse infiltration of the frontal and temporal lobes of the right hemisphere, brainstem, and the leptomeninges covering the whole spinal cord by an astrocytic tumor, which showed features both of low-grade astrocytoma and glioblastoma multiforme. No mutations in the p53 and PTEN tumor suppressor genes were found; immunoreactivities for p53, PTEN, and EGFR could not be detected.     

Type and frequency of gynecological tumors in the Gondar region of Ethiopia

The present work was done to examine the type and frequency of benign and malignant gynecological tumors in patients treated during the 5 years period from 1982 to 1986 in the Gondar College of Medical Sciences. The different pathohistological findings were compared with the history and chief complaints of the patients. A total number of 208 patients with benign and of 93 patients with malignant tumors could be analyzed. In the group of benign tumors we observed most frequently breast tumors (25.5%), endometrial and cervical polyps (24.5%), and myoma uteri (23.1%). Patients with benign ovarian tumors were treated in 40 (19.2%) cases. In the group of malignant tumors we have seen breast carcinomas (31.2%) and cervical carcinomas (34.4%) most frequently followed by the endometrial (13.0%) and ovarian (11.8%) neoplasms. Comparison with the data of the literature has shown that the mean age of our patients is lower and the number of women with advanced carcinomas is higher than in other reports.     

Immunohistochemical expression of P-glycoprotein and glutathione S-transferases in cerebral gliomas and response to chemotherapy

The expression of the drug resistance-related proteins glutathione S-transferases (GST) and P-glycoprotein (Pgp) was analyzed quantitatively in samples of 53 astrocytic gliomas (eight WHO grade 1, 11 WHO grade 2, 9 WHO grade 3 and 25 glioblastomas, WHO grade 4). Sections of these tumors were immunohistochemically stained with antibodies to Pgp (MDR1-gene product) and to GST subclasses alpha, mu and pi. Pgp expression was not detected in tumor cells of the majority of low-grade astrocytomas (69%) and the percentage of Pgp stained cells generally increased with tumor grade. However, 4 of the 34 malignant gliomas were negative. Many neoplastic cells of most tumors were dominantly stained for GST-pi. The other two subclasses were expressed in a less consistent fashion with no linear correlation to grading. Grade 2 astrocytomas exhibited the highest percentage of cells with GST expression. GST-alpha was absent in 9 tumors, GST-mu in 8 and GST-pi in 4. Four tumors showed no expression of any GST subclass or Pgp in neoplastic cells. Of 13 patients 5 with a more favorable clinical course after radiation and chemotherapy had a lower percentage of neoplastic cells immunostained for Pgp and the three GST subclasses than 8 patients with a worse clinical course. These results suggest a relationship between expression of drug resistance-related proteins in gliomas and response to chemotherapy with ACNU/VM26. Received: 18 November 1996 / Revised: 5 May 1997 / Revised, accepted: 16 June 1997     

Assessment of tumor cell invasion factors in gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare brain tumor characterized by widespread infiltration of large parts of the brain and sometimes even the spinal cord. To determine the cause of this extraordinary degree of brain invasion, we studied immunoexpression of factors associated with brain infiltration in low-grade and high-grade tumor samples from nine GC cases. We further determined the allelic status of the fibroblastic growth factor receptor 4 (FGFR4) gene at position 388 (arginine [Arg³⁸⁸] or glycine [Gly³⁸⁸]) in eighteen GC patients, because the presence of at least one Arg³⁸⁸ allele has been suggested to favor tumor cell motility compared to tumor cells homozygeous for the Gly³⁸⁸ allele. Immunohistochemical analyses showed that tumor samples from three GC cases expressed Tenascin-C, whereas six cases had CD44 - immunopositive tumor samples. Expression of MMP-9 was not observed in any of the nine GC patients. FGFR4 genotyping revealed the presence of the Arg³⁸⁸ in 72% of the eighteen GC cases, a frequency similar to the one found in 21 common astrocytomas (71%). In tumor-free control DNA, the Arg³⁸⁸ phenotype was present in 60%. These data indicate that CD44 expression might be related to the tumor infiltration in GC, and that patients suffering from GC or other common astrocytomas do not have a significantly increased frequency of the tumor cell motility-favoring Arg³⁸⁸ FGFR4 allele.     

Distribution of p53 alterations in a case of gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare neuroepithelial tumor characterized by diffuse infiltration of large parts of the brain. The origin of GC is unknown, and the molecular alterations underlying this tumor have not been determined. Because mutations in the p53 tumor-suppressor gene are frequent in common gliomas, we investigated the distribution of p53 alterations by immunohistochemistry and direct sequencing in a GC case with a disease involving both hemispheres and the basal ganglia. Nuclear accumulation of p53 protein was detected in a single region with features of a high-grade glioma. In the remaining 10 regions, corresponding to low-grade gliomas, no p53 accumulation was seen. In 1 low-grade tumor sample, a pathogenic splice site mutation was detected. These findings suggest that p53 alterations occur in GC, but are no prerequisite of malignant progression. The distribution of p53 alterations demonstrates the existence of topographically different clones in 1 patient.