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.
A woman with typical features of myoclonic epilepsy with ragged red fibers (MERRF) had a novel heteroplasmic mutation (G611A) in the mitochondrial DNA tRNA phenylalanine gene. The mutation was heteroplasmic (91%) in muscle but undetectable in accessible tissues from the patient and her maternal relatives. Single-fiber PCR analysis showed that the proportion of mutant genomes was higher in cytochrome c oxidase (COX)-negative ragged red fibers (RRFs) than in COX-positive non-RRFs. This report shows that typical MERRF syndrome is not always associated with tRNA lysine mutations.
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.
Malignant transformation occurs in 1.5-2% of mature cystic teratomas (MCT)s of the ovary and usually consists of squamous cell carcinoma, whereas other malignancies are less common. Diagnosis and treatment represent a challenge for gynecologic oncologists. The preoperative detection is very difficult and the diagnostic accuracy of imaging examinations is uncertain. The tumor is usually detected post-operatively based on histopathologic findings. This paper reviewed 206 consecutive patients who underwent surgery for a histologically-proven MCT of the ovary between 2010 and 2017. Malignant transformation occurred in 3 (1.5%) of them, and consisted of squamous cell carcinoma in one, type 2 papillary renal carcinoma in one, and papillary thyroid carcinoma in another one. The paper reported the clinical, radiological and histological features of these cases and reviewed the literature data on the treatment options.
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