Much of the morbidity of intracranial meningiomas is related to the degree of tumour vascularity and the extent of peritumoural vasogenic oedema. Several studies have shown that vascular endothelial growth factor (VEGF) is up-regulated in meningiomas, although its relationship with tumour vasculature is still unclear. In order to better understand the angiogenic assessment of intracranial meningiomas, we analysed its vascular pattern, both as number and as morphologic configuration of microvessels. Moreover, we investigated the mRNA-VEGF expression, relating this expression to vascular pattern. A total of 40 intracranial meningiomas, classified as benign (31 cases), atypical (7 cases), and anaplastic (2 cases) were analysed. RT-PCR analyses of mRNA-VEGF and competitive-PCR were performed. VEGF expression and microvessel density (MVD) were also immunohistochemically investigated. Grade II-III meningiomas showed numerous small microvessels (mean: 34), while the majority of Grade I showed few larger vessels (mean: 13.09) (P = 0.000003). A microvessel pattern overlapping into atypical subtype was found in eignt of the 31 (25.8%) Grade I meningiomas. A significant association was found between grading and vascular pattern (P = 0.0002), as well as between the MVD and the immunohistochemical expression of VEGF (P = 0.0005). The expression of mRNA agreed with the immunohistochemical expression of the protein (P < 0.0001). A total of 39 cases expressed the 121 VEGF isoform and, among these, 28 cases also expressed the 165 isoform. Only 9 cases expressed both isoforms 165 and 189. Grade II and III meningiomas showed a preponderant expression of soluble isoforms (121 and 165). These results prompt us to speculate that the microvessel pattern could underlie a higher metabolic demand, probably due to a rapid growth with a consequent worse clinical behaviour of the tumour. In this sense, the vascular pattern may be used as a prognostic factor, in order to mostly focus attention on those Grade I meningiomas which have a higher likelihood of either recurrence or development of perilesional oedema. The pattern of vasculature itself seems to be dependent on the types of VEGF isoforms: the Grade II-III meningiomas (that presented numerous microvessels) expressed the soluble isoforms 121 and 165, while the isoform 189 was more frequently detected in Grade I meningiomas.

Our results provide oncologists with a highly accurate laboratory method to identify biological predictors of the efficacy of different therapies, and they may have an important impact on clinical practice. This method may be particularly useful in patients with advanced/metastatic NSCLC.

Purpose: The c-kit protein, also known as CD117, is a member of the type III receptor tyrosine kinase family. Kinase activity has been implicated in the pathophysiology of many tumors, including small-cell lung carcinoma (SCLC). Autocrine or paracrine activation of c-kit by its ligand has been postulated for lung cancer, but this receptor can also be activated by mutations of the c-kit gene. We examined c-kit expression and mutational status in SCLC to verify its putative expression and genetic alterations, as well as its eventual prognostic impact.Experimental Design: We studied 60 SCLC samples to determine the mutations of the coding region of the gene; the exons 9 and 11 were analyzed by PCR-single-strand conformational polymorphism and automated sequencing. Moreover, c-kit expression was evaluated in 55 samples by immunohistochemical method.Results: Expression of c-kit was demonstrated in about 40% of SCLC samples. Two mutations in exon 9 and three mutations in exon 11 were found. Kaplan-Meier analysis revealed no prognostic significance of c-kit expression for survival.Conclusions: In our series, the expression of c-kit and its mutational status failed to appear relevant or to have a significant impact on survival; this makes the therapeutic approach with an inhibitor of tyrosine kinase more difficult in SCLC until a sure demonstration of c-kit implication is obtained for this tumor.

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Human telomerase is a structurally complex ribonucleoprotein that is responsible for the maintenance of telomeric DNA at the ends of the chromosomes. The enzyme is proposed as having an important role in cell immortalization and oncogenesis. A limited number of studies have been performed on the telomerase system in brain tumors, and these studies are somewhat conflicting. The relative ineffectiveness of current therapies for malignant gliomas led to the need for novel targets for more promising approaches. In order to clarify the prognostic significance of telomerase expression in gliomas and to speculate on therapeutic implications, we examined telomerase activity by the telomeric repeat amplification protocol (TRAP) assay in 42 gliomas, (32 multiform glioblastomas, 4 anaplastic astrocytomas, 4 differentiated astrocytomas, 1 oligoastrocytoma and 1 oligosarcoma). Telomerase messenger expression (hTERT mRNA) was evaluated by reverse transcription-PCR analysis in the same group of tumors. High telomerase activity was detected in 21/42 gliomas (50%). The levels of telomerase in terms of its messenger level expression overlapped the activity; in fact, a significant association between telomerase activity and hTERT mRNA expression was found (¯2 test; p<0.0001). At univariate analysis, advanced age as well as high telomerase activity and hTERT mRNA levels were seen to be significant predictors of worse prognosis regarding both overall survival (p=0.007, p=0.007, p=0.04, respectively) and disease-free interval (p=0.008, p=0.008, p=0.04, respectively). All these variables maintained a significant independent prognostic role in multivariate analysis. Telomerase may represent an indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.