The involvement of circulating microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated; however, little is known about circulating miRNA profiles in astrocytomas. In our study, we performed genome-wide serum miRNA analysis by the Solexa sequencing followed by validation conducted in the training and verification sets with a stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay from serum samples of 122 untreated astrocytomas patients (WHO grades III-IV) and 123 normal controls. Identified miRNAs were subsequently examined in 55 grade II, 15 grade I astrocytomas, 11 astrogliosis, 42 other primary brain tumors and 8 tumor tissues from grades II-IV astrocytomas. In addition, paired serum samples before and after operation were collected from 14 malignant astrocytomas to determine the effect of surgery on the miRNAs' levels. A marked difference in serum miRNA profile was observed between high-grade astrocytomas and normal controls. Seven miRNAs were validated by RT-qPCR assay to be significantly decreased in grades II-IV patients (p < 0.001), including miR-15b * , miR-23a, miR-133a, miR-150 * , miR-197, miR-497 and miR-548b-5p, and the seven-miRNA panel demonstrated a high sensitivity (88.00%) and specificity (97.87%) for malignant astrocytomas prediction. These identified miRNAs also exhibited a global decrease in tumor tissues relative to normal tissues. Furthermore, these miRNAs in serum were markedly elevated after operation (p < 0.001). In addition, some of these serum miRNAs were significantly different between malignant and benign cases, astrogliosis and other primary brain tumors. The seven serum miRNAs identified in our study hold potential as noninvasive biomarker for malignant astrocytomas.Astrocytomas are the most common primary brain tumors arising from astrocytes, the most abundant type of glial cells of the central nervous system or, more likely, from resident cancer stem cells. Based on their histology and morphological features, astrocytomas are divided into four clinical grades 1 : Grade I (including pilocytic astrocytomas and subependymal giant cell astrocytoma) comprises slowly growing benign astrocytomas, grade II (diffuse astrocytomas and pleomorphic xanthoastrocytoma) represents the least malignant cases and grades III (anaplastic astrocytomas) and IV (glioblastomas or GBM) are highly malignant and have some of the worst survival rates of all human cancers. 1,2 Grade II tumors have an inherent tendency to spontaneously progress to grades III or secondary IV. 1 Surgery followed by chemoradiotherapy is the mainstream of primary grade IV astrocytomas treatment. In the course of postradiation events, however, it is sometimes difficult for neurosurgeons, radiologists and pathologists to discriminate tumor recurrence from radiation necrosis which usually results in astrogliosis. 3,4 Despite the recent advances in therapeutic strategies, such as surgical resection and adjuvant radiotherapy and chemotherapy, the 5-year ...

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer predisposition syndrome, characterized by development of a variety of neoplasms in multiple organs. Central nervous system hemangioblastoma (CHB) is the most common manifestation of VHL disease. The germline mutations in the VHL tumor suppressor gene are responsible for the inherited cancer predisposition syndrome. To expand the VHL mutation data and to investigate the tumorigenesis of VHL-associated CNS hemangioblastoma, 24 CHB tissue samples and blood samples of 14 patients from 10 Chinese VHL families were collected and subjected to molecular genetic analysis. Six distinctive germline mutations were identified, and the 601 G to C (Val130Phe) mutation is reported for the first time. Somatic mutations analysis of the VHL gene in VHL-associated CHB showed that loss of heterozygosity (LOH) occurred in more than half of the cases. In addition, expression of the ZAC1 tumor suppressor gene protein was studied using immunohistochemistry staining in CHB tissues with a specific polyclonal antibody. The ZAC1 protein was lost in all CHB. Our data exhibited high frequency of LOH of ZAC1 gene in VHL-associated CHB, indicating that ZAC1 may have a role in tumorigenesis of VHL-associated CHB.

Multiple vascular patterns are presented in tumors of the central nervous system (CNS), including microvascular hyperplasia, branching capillaries, numerous capillaries without definite pattern, hyalinized vessels, and angiomatous area. These vascular patterns play important roles in pathological diagnosis of brain tumors. Because of insufficient recognition of the significance of the various vascular patterns, only a few of them have been applied in pathological diagnosis, leading to missed diagnosis and diagnostic errors. Microvascular hyperplasia can present in multiple brain tumors but display different diagnostic values. Otherwise, varied brain tumors characterized by branching capillaries or vascular pattern mimicking branching capillaries should be given careful consideration. Therefore, a familiarity of these tumors and their vascular pattern is essential for general pathologists. This study reviews the value of various kinds of vascular patterns for pathological diagnosis of brain tumors, constructs a framework for better understanding, and provides a novel perspective for general pathologists.