cyclin-d1 and Meningeal-Neoplasms

Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype.

Topics: Adult; Brain Neoplasms; Case-Control Studies; Cyclin D1; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Glioma; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Staging; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Prognosis; Risk Factors

Cyclin D1 has been reported overexpressed in many malignant cancers. However, the expression pattern and biological function of cyclin D1 in meningiomas are still unknown. In this study, we examined the expression of cyclin D1 in meningioma with immunohistochemistry and correlated the measure to the recurrence. Potential effects of cyclin D1 on tumor growth and apoptosis were also examined in representative cell lines (IOMM-Lee and CH157) by inhibiting cyclin D1 with RNA interference. We demonstrate that cyclin D1 mRNA and protein expression are positively correlated with meningioma grade and that higher cyclin D1 expression correlates with higher recurrence. Knockdown of cyclin D1 by the siRNA decreased IOMM-Lee and CH157 cell proliferation, promoted the rate of apoptosis and attenuated invasive capacity. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that cells stably underexpressing cyclin D1 showed lower expression of survivin and the antiapoptotic protein B cell lymphoma-2 (Bcl-2) compared to control cells. These results indicate that high cyclin D1 expression is associated with a poor outcome of meningioma patients and knockdown of cyclin D1 expression may be a potential treatment for malignant meningioma.

Topics: Apoptosis; Biomarkers, Tumor; Blotting, Western; Cell Cycle; Cyclin D1; Gene Knockdown Techniques; Humans; Immunohistochemistry; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Transfection; Up-Regulation

Meningiomas are slow-growing neoplasms that recur locally. Their morphologic grading does not always correlate with patient outcome. We evaluated the status of several immunohistochemical markers with histopathologic parameters in various grades of meningioma.Eighty-eight meningioma specimens were examined immunohistochemically to determine the status of Ki-67, cyclin D1, epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and bcl-2. Several clinical and pathological parameters were investigated.Forty-nine Grade I, 33 Grade II, and 6 Grade III meningiomas were observed. VEGF and Ki-67 expression was correlated with higher tumor grade. The association between grade and other immunohistochemical markers expression was not significant. A correlation was observed between COX-2 expression and invasiveness to the brain or adjacent soft tissue. Tumor recurrence was correlated with brain or adjacent soft tissue invasion. We also observed a relationship between VEGF level and COX-2 expression, and they were both correlated with necrosis.Immunohistochemical evaluation of VEGF, COX-2, and Ki-67 expression can provide information regarding the behavior of meningiomas, particularly for cases in which histological grading is not straightforward.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cyclin D1; Cyclooxygenase 2; ErbB Receptors; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins c-bcl-2; Vascular Endothelial Growth Factor A; Young Adult

Papillary meningioma (PM) is an uncommon meningioma subtype, and the clinical characteristics remain unclear.. To determine the clinical characteristics and prognosis of PM.. The clinical data of 30 PM patients were collected, the samples were reexamined, and the patients' prognoses were based on clinical observations and calculated according to the Kaplan-Meier method.. The 30 patients included 16 males and 14 females (median: 34.0 years upon initial diagnosis). Of the 48 intracranial operations in the 30 patients, total removal was attained in 34 surgeries, and subtotal removal in 14 surgeries. Radiotherapy was provided in 20 patients. In 40 specimens with follow-up, 29 attained the positive aggressive factors. Six tumors showed positive progestogen receptor (PR) combined with negative Bcl-2. The median follow-up period was 39.0 months. Tumor recurrence occurred in 18 patients (median: 17.0 months); the recurrence rates following total removal and subtotal removal were 57.1% and 100%, respectively. Fourteen patients died of the recurrence. In the univariate analyses, positive aggressive factors (P = .021), positive PR combined with negative Bcl-2 immunoreactivity (P = .011), the extent of resection (P = .001), and radiotherapy (P = .002) were significantly related to progression-free survival. The MIB-1 labeling index was not significantly related to progression-free survival (P = .88).. PM is a rare subtype of meningioma with a tendency of recurrence. The extent of resection is an important prognosis factor. The presence of positive histopathological index increases the recurrence risk. Positive PR combined with negative Bcl-2 immunoreaction might predict a good prognosis. Postoperative radiotherapy may play a vital role in prolonging the time to tumor recurrence.

Topics: Adolescent; Adult; Aged; Antigens, CD; Cerebral Cortex; Child; Child, Preschool; Cyclin D1; ErbB Receptors; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Mucin-1; Nerve Tissue Proteins; Receptors, Steroid; Retrospective Studies; Young Adult

Mantle cell lymphoma (MCL) is an uncommon type of gastrointestinal lymphoma. MCL is a distinct subtype of B-cell non-Hodgkin lymphomas. The major subtype of MCL is characterized by the presence of multiple lymphomatous polyposis (MLP), in which multiple polyps are observed along the gastrointestinal tract. The malignant cells express pan B-cell marker and the T-cell marker cluster of differentiation 5. The chromosomal translocation t(11;14)(q13;q32) that causes cyclin D1 overexpression is commonly observed on the cytogenetic analysis of MCL. Survival improvement has recently been achieved for patient with MCL by the successful introduction of monoclonal antibodies and dose-intensified approaches for treatment, including autologous stem cell transplantation strategies. Some reports suggest that there is an increased incidence of second malignancies in patients with MCL or lymphoma. We report a case of MCL involving the colon; the patient was a 60-year-old man who complained of low abdominal discomfort during defecation. During the workup, a meningioma was unexpectedly discovered. On analysis, the tumor was found to be a t(11;14)-negative and non-MLP-type MCL.

Topics: Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; Humans; Lymphoma, Mantle-Cell; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Positron-Emission Tomography; Translocation, Genetic

Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of beta-catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target beta-catenin mRNA, thereby inhibiting its translation and blocking Wnt/beta-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of beta-catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/beta-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas.

Topics: Apoptosis; Base Sequence; beta Catenin; Cadherins; Cell Proliferation; Chromosome Deletion; Chromosomes, Human, Pair 1; Comparative Genomic Hybridization; Cyclin D1; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Meningeal Neoplasms; Meningioma; MicroRNAs; Molecular Sequence Data; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Tumor Cells, Cultured; Up-Regulation; Wnt Proteins

Cyclin D1 is an important nuclear protein required for progression of cells through the G1 phase of the cell cycle. The proliferative potential of meningiomas has been studied using various proliferative markers. However, there have been only few published studies evaluating Cyclin D1 immunoreactivity in meningiomas.. The aim of our study was to analyze the Cyclin D1 expression in meningiomas and correlate it both with proliferation markers Ki67 and PCNA, and with meningiomas of WHO grade.. We evaluated immunoreactivity for proliferative markers (Cyclin D1, Ki-67, and PCNA) in a consecutive series of 64 meningioma samples obtained from patients who underwent surgical resection because of cerebral or spinal meningiomas. Immunohistochemical staining with Ki-67, PCNA, and Cyclin D1 was performed using the microwave processing procedure and LSAB+ methodology. The number of positive cells for each antibody has been determined and shown in percentage in relation to 1000 counted cells.. All meningioma samples showed immunostaining for Ki-67, PCNA, and Cyclin D1 antibodies. The Cyclin D1 scores exhibited a close correlation with Ki-67 and PCNA immunostaining (P < 0.01). Some meningiomas (15 cases) showed a combination of nuclear and cytoplasmatic (fine granular) Cyclin D1 immunoreactivity. All proliferative indexes have been in positive correlation with meningioma grade.. Our comparative study of proliferative markers in meningiomas demonstrated Cyclin D1 as a very useful proliferative marker in meningiomas.

Topics: Biomarkers, Tumor; Cell Proliferation; Cyclin D1; Humans; Immunohistochemistry; Ki-67 Antigen; Meningeal Neoplasms; Meningioma; Proliferating Cell Nuclear Antigen

To investigate the methylation of p16(INK4a) and RB gene, and the expression of p16(INK4a) in meningiomas.. Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation of p16(INK4a) and RB in 50 cases of meningiomas, and immunostaining was performed to analyze the protein expression of p16(INK4a) in 25 of those cases.. No methylation was found in the benign meningiomas, whereas methylation of p16(INK4a)or RB occurred in 6(37.5%) cases of grade II tumors and 4(28.6%) cases of grade III tumors, and among these cases, an atypical meningioma showed methylation of both genes. Thirteen cases showed p16(INK4a) positive expression, but none of them was methylated.. The methylation of p16(INK4a) or RB is related with the tumorigenesis and progression of atypical and anaplastic meningiomas, and a probable mechanism is that methylation causes the loss of expression and leads to dysfuncation of the p16(INK4a)/cyclin D1/CDK4/RB pathway.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; DNA Methylation; Female; Genes, p16; Genes, Retinoblastoma; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Proto-Oncogene Proteins

While several genetic alterations associated with the evolution of the astrocytomas have been identified, the molecular basis of non-astrocytic brain tumors has remained largely unknown. In this study, p15, p16, CDK4 and cyclin D1 genes were analyzed in 69 nonastrocytic human brain tumors, including 17 oligodendrogliomas, 16 medulloblastomas/primitive neuroectodermal tumors (PNETs), 14 ependymomas and 22 meningiomas. Southern blot analysis of DNA from frozen samples showed no homozygous deletions in p15 or p16 genes in any of these tumors. No mobility shift was found by PCR-single-strand conformation polymorphism (PCR-SSCP) analysis in exons 1 and 2 of the p15 gene and exons 1 and 2 of the p16 genes, except for one oligodendroglioma. Direct sequencing of DNA from this tumor showed a G --> A transition at nucleotide 436 (codon 140) in exon 2 of the p16 gene, which is a common polymorphism. Southern blot analyses revealed no amplification of CDK4 and cyclin D1 genes in any of the neoplasms analyzed. In contrast to astrocytic brain tumors, which show frequent loss of the p16 gene and amplification of the CDK4 gene, alteration of these genes appears to be rare in other neoplasms of the human nervous system.

Topics: Astrocytoma; Base Sequence; Blotting, Southern; Brain Neoplasms; Cerebellar Neoplasms; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Cyclins; DNA Primers; Ependymoma; Humans; Medulloblastoma; Meningeal Neoplasms; Meningioma; Molecular Sequence Data; Neuroectodermal Tumors; Oligodendroglioma; Oligonucleotide Probes; Oncogene Proteins; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proto-Oncogene Proteins; Reference Values