Purpose: The receptor tyrosine kinase Axl has recently been identified as a critical element in the invasive properties of glioma cell lines. However, the effect of Axl and its ligand growth arrestŝ pecific gene 6 (Gas6) in human gliomas is still unknown. Experimental Design: Axl and Gas6 expression was studied in 42 fresh-frozen and 79 paraffinembedded glioma specimens by means of reverse transcription-PCR and immunohistochemistry. The prognostic value of Axl and Gas6 expression was evaluated using a population-based tissue microarray derived from a cohort of 55 glioblastoma multiforme (GBM) patients.Results: Axl and Gas6 were detectable in gliomas of malignancy gradesWHO 2 to 4. Moderate to high Axl mRNA expression was found in 61%, Axl protein in 55%, Gas6 mRNA in 81%, and Gas6 proteinin 74% of GBMsamples, respectively. GBM patients withhigh Axl expression and Axl/Gas6 coexpression showed a significantly shorter time to tumor progression and an association with poorer overall survival. Comparative immunohistochemical studies showed that Axl staining was most pronounced in glioma cells of pseudopalisades and reactive astrocytes. Additionally, Axl/ Gas6 coexpression was observed in glioma cells and tumor vessels. In contrast, Axl staining was not detectable in nonneoplastic brain tissue and Gas6 was strongly expressed in neurons.Conclusions: In human gliomas, Axl and Gas6 are frequently overexpressed in both glioma and vascular cells and predict poor prognosis in GBM patients. Our results indicate that specific targeting of the Axl/Gas6 signaling pathway may represent a potential new approach for glioma treatment.

This study correlates the histopathological classification of meningiomas with clinicopathological features of biological activity. A retrospective evaluation of 1799 surgical specimens of meningiomas from 1582 patients was made. The classic histopathological type, atypical meningiomas defined by increased cellularity and at least five mitotic figures in 10 high-power fields, anaplastic (malignant) meningiomas, and hemangiopericytic or papillary meningiomas were seen in 87.6%, 7.2%, 2.4%, and 2.8% of operations, respectively. The rates of recurrence in surgically treated patients with classic, atypical, anaplastic, and hemangiopericytic or papillary meningiomas were 6.96%, 34.6%, 72.7%, and 68.2%, respectively. The extent of surgery and the tumor size and site were studied in detail in 252 tumors of all histopathological types. Recurrences were rare in classic meningiomas after complete resection, whereas atypical and anaplastic tumors recurred after complete resection much more frequently. Classic meningiomas, hemangiopericytomas, and papillary meningiomas were smaller at surgery than atypical and malignant meningiomas. Atypical and malignant tumors were operated on more often in falcine and lateral convexity regions than were classic meningiomas. To support the authors' subjective categorization by a quantitative parameter related to proliferation, 112 meningiomas comprising all histopathological subtypes were investigated for staining of argyrophilic nucleolar organizer region proteins (Ag-NOR's). The Ag-NOR counts showed significant differences between classic, atypical, and anaplastic tumors but no significant differences between primary and recurrent tumors. Hemangiopericytomas and papillary meningiomas had lower Ag-NOR values than anaplastic meningiomas. A correlation of Ag-NOR numbers with the authors' histopathological scale of malignancy supports the introduction of atypical meningiomas with intermediate biological behavior on the classification scale between classic and anaplastic meningiomas. Overlapping of Ag-NOR numbers among all groups of malignancy may restrict the prognostic value of Ag-NOR counting in the individual case.

In Austria, registration of malignant brain tumours is legally mandatory, whereas benign and borderline tumours are not reported. The Austrian Brain Tumour Registry (ABTR) was initiated under the auspices of the Austrian Society of Neuropathology for the registration of malignant and non-malignant brain tumours. All Austrian neuropathology units involved in brain tumour diagnostics contribute data on primary brain tumours. Non-microscopically verified cases are added by the Austrian National Cancer Registry to ensure a population-based dataset. In 2005, we registered a total of 1,688 newly diagnosed primary brain tumours in a population of 8.2 million inhabitants with an overall age-adjusted incidence rate of 18.1/100,000 person-years. Non-malignant cases constituted 866 cases (51.3%). The incidence rate was higher in females (18.6/100,000) as compared to males (17.8/100,000), while 95/1,688 (5.6%) cases were diagnosed in children (<18 years). The most common histology was meningioma (n = 504, 29.9%) followed by glioblastoma (n = 340, 20.1%) and pituitary adenoma (n = 151, 8.9%). Comparison with the Central Brain Tumor Registry of the United States (CBTRUS) database showed high congruency of findings. The ABTR model led by neuropathologists in collaboration with epidemiologists and the Austrian National Cancer Registry presents a cooperative way to establish a population-based brain tumour registry with high quality data. This setting links cancer registration to the mission of medical practice and research as defined by the World Medical Association in the Declaration of Helsinki. The continued operation of ABTR will aid in monitoring changes in incidence and in identifying regional disease clusters or geographic variations in brain tumour morbidity/mortality.

Summary The bcl-2 gene encodes for a mitochondrial membrane proto-oncoprotein, the expression of which is known to suppress programmed cell death (apoptosis). In the present study the