Takafumi Nishizaki

Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization

Comparative genomic hybridization (CGH) is a technique that allows the detection of losses and gains in DNA copy number across the entire genome. We used CGH to study the genetic alterations that occur in primary astrocytomas, including 14 glioblastomas (GBM), 12 anaplastic astrocytomas (AA), and 7 low‐grade astrocytomas (LGA). The average numbers of total aberrations in GBM, AA, and LGA were 9.7, 5.4, and 4.0, respectively. The average number of DNA sequence losses in GBM was significantly higher than that in AA or LGA (P < 0.01). Frequently altered regions (> eight cases) observed in all grades of astrocytoma were 7p13‐p12 (gain), 7q31 (gain), 8q24.1‐q24.2 (gain), 9p21 (loss), 10p12‐p11 (loss), 10q22‐qter (loss), 13q21‐q22 (loss), and 20q13.1‐q13.2 (gain). Loss of 9p, 10p, or 10q, and the gain or amplification of 7p, were observed frequently in GBM (64%, 57%, 64%, and 50% of cases, respectively). Frequent alterations found in AA were losses of 9p, 10q, and 13q, and gains of 1q, chromosome 7, 11q, and Xq. Whereas 7p13‐p11 amplification occurred exclusively in cases with the loss of all or part of chromosome 10, this change never occurred in cases having an increase in copy number of 8q, which was the most frequent change observed in LGA (four of seven cases). These results may indicate that an increase in copy number of 8q is an important event in GBM, with a genetic pathway, which is distinct from that in GBM with 7p amplification. Genes Chromosomes Cancer 21:340–346, 1998.

Comparative genomic hybridization analysis of genetic alterations associated with malignant progression of meningioma.

Little is known about genetic alterations during malignant progression of meningioma. We used comparative genomic hybridization (CGH) in 20 patients (13 with typical, 4 with atypical and 3 with anaplastic meningiomas) to investigate the genetic pathway underlying the development of meningioma. Typical meningiomas displayed only a few genetic changes such as monosomy 22. Anaplastic meningiomas manifested more aberrations than typical meningiomas, frequently exhibiting losses of 1p, 2p, 6q, chromosome 10 and 14q, and gain of 20q, in addition to monosomy 22. The average number of alteration sites in each patient with typical meningioma was significantly less than those in each patient with atypical (p<0.01) and with anaplastic meningioma (p<0.05). Anaplastic meningiomas showed the chromosomal changes seen in atypical meningiomas together with other aberrations. These CGH findings suggest that losses of 1p, 2p, 6q, chromosome 10 and 14q, and gain of 20q are genetic changes implicated in the malignant progression of meningioma.

Nucleolar Organizer Regions in Meningioma

Seventy-eight cases of meningioma and related tumors were examined independently using a simple and reproducible argyrophilic method for the demonstration of nucleolar organizer regions (AgNORs) and staining with bromodeoxyuridine monoclonal antibody. The mean number of AgNORs per cell and the bromodeoxyuridine labeling index were shown to be linearly related (r = 0.84, P less than 0.001). The mean AgNOR number was 2.99 for meningeal sarcoma, 2.29 for anaplastic meningioma, 2.08 for hemangiopericytic meningioma. 1.72 for recurrent meningioma without atypical histological findings, and 1.52 for nonrecurrent meningioma. We noted that the mean number of AgNORs reflected the cellular kinetics of a tumor and was related to histological grade and clinical behavior.

Distinct primary central nervous system lymphoma defined by comparative genomic hybridization and laser scanning cytometry

We investigated chromosomal alterations using comparative genomic hybridization (CGH), and DNA ploidy patterns using laser scanning cytometry (LSC) in 8 primary central nervous system lymphomas (PCNSLs). The average number of chromosomal alterations detected by CGH was 6.9 (gain: 4.1, deletion: 2.8). Frequent alterations were gains of chromosomes 12, 18q, and X, and deletion of 6q, which were similar to those seen in non-CNS diffuse large B-cell lymphoma. DNA aneuploidy was detected by LSC in 4 of the 8 cases. The DNA aneuploid lymphomas had more chromosomal alterations than the DNA diploid ones (9.3 vs. 4.5, P <.05). The former had higher MIB-1 indices than the latter. The present investigation indicates that although most of the PCNSL are histologically uniform, they are divided cytogenetically into DNA aneuploid and diploid tumors.

Cytogenetic Alterations in Pituitary Adenomas Detected by Comparative Genomic Hybridization

Pituitary adenomas are benign monoclonal tumors that are either hormonally functional or nonfunctional. Although their histologic and immunocytologic characteristics have been studied extensively, cytogenetic studies are scarce. We have investigated the cytogenetic alterations and DNA ploidy patterns of 12 sporadic pituitary adenomas, including 2 growth-hormone-secreting tumors, 1 prolactinoma, and 9 nonfunctional adenomas, by comparative genomic hybridization (CGH) and laser scanning cytometry (LSC). CGH revealed that the mean number of sites of copy gain was significantly higher in functioning adenomas than in nonfunctioning tumors (P < 0.01). The most frequent change detected was loss of 13q (5 cases), with a minimal common overlapping region at 13q14. These findings suggest that a putative tumor suppressor gene on 13q14 may play an important role in the development of pituitary adenomas. DNA aneuploidy was detected by LSC in 3 of the 12 cases. The DNA aneuploid adenomas showed cytogenetic changes more frequently than did the DNA diploid tumors (P < 0.02).

Prognostic implications of meningiomas in the elderly (over 70 years old) in the era of magnetic resonance imaging.

SummaryDuring the 5 years from 1987 to 1991, 89 elderly patients, aged 70 years and over, were admitted to departments of neurosurgery in Yamaguchi prefecture with meningioma. The clinical features and prognostic implications of meningioma in the elderly were assessed retrospectively. Seventy-eight (88%) of the 89 patients underwent surgery, which was a higher rate than has been previously reported. The length of clinical history was also shorter than in previous studies, and was partly due to the recent introduction of magnetic resonance imaging (MRI). The incidence of poor prognosis (severe disability, vegetative or dead) in the elderly and a younger group aged less than 70 years was 13% and 7%, respectively, but the difference was not statistically significant. In the surgically treated elderly group, age did not influence the patients outcome. The factors affecting the outcome were pre-operative neurological deficit (p<0.05), histological malignancy (p<0.05), and multiple operations (p<0.05). Twenty-seven of the elderly meningioma patients were in good physical condition with minimal neurological involvement. They underwent total removal of the tumour at the first operation, and the histological diagnosis was benign. Twenty-five of these 27 patients fell into the best outcome category. Therefore, age alone was not a factor preventing proper surgical treatment of meningioma in the elderly.

Idiopathic cranial pachymeningoencephalitis focally affecting the parietal dura mater and adjacent brain parenchyma: case report.

OBJECTIVE AND IMPORTANCE Cranial pachymeningitis is a typically diffuse granulomatous disease, which often affects the tentorium and falx. We report a rare case of idiopathic cranial pachymeningoencephalitis focally affecting only the left parietal dura mater and adjacent inferior parietal lobule. CLINICAL PRESENTATION A 46-year-old woman, with no history of disease, suddenly had a generalized convulsion. A gadolinium-enhanced T1-weighted magnetic resonance image showed homogeneously stained meninges extending to the cortical parenchyma with marked perifocal edema. The thickened dura was visualized as a hypointense area on a T2-weighted magnetic resonance image. INTERVENTION The patient underwent successful en bloc excision of the mass involving the dura mater and adjacent brain parenchyma. Histological examination of the dura mater revealed large numbers of chronic and acute inflammatory cells. These cells were also present in the subarachnoid and Virchow-Robin spaces and part of the brain parenchyma in the resected cortex. After the operation, the patient experienced no neurological deficits or recurrent mass for 10 months. CONCLUSION Early diagnosis of pachymeningitis using magnetic resonance imaging is important for the treatment of pachymeningoencephalitis, because diffuse involvement of the dura mater and brain parenchyma can make en bloc excision difficult.

Genetic Alterations in Pediatric Medulloblastomas Detected by Comparative Genomic Hybridization

Children with medulloblastomas show diverse clinical courses even when receiving similar treatments. In this study, comparative genomic hybridization, which allows the detection of losses and gains in DNA copy number along the entire genome, was used to investigate the genetic alterations in 6 cases of medulloblastoma with adequate follow-up periods and similar treatments, and in a medulloblastoma cell line. In the cell line, the number of aberrations was the highest of all samples examined. In 6 clinical samples, frequently altered regions (more than 3 cases) observed in all medulloblastomas were gains of 7q and 17q (4 cases each), and of 2p, 2q and 7p (3 cases each). High-grade amplification was observed at the loci 8q, 17q and 21q, each in a single case. The case with the most favorable outcome 9 years after surgery had the smallest number of chromosomal changes among the cases examined. Our results may indicate that further acquisition of genetic alterations detected by comparative genomic hybridization are associated with unfavorable prognosis in patients with medulloblastomas.

Transferrin receptors in injured brain

SummaryRecent studies have demonstrated the presence of transferrin receptors (Tf-R) in the central nervous system. The present study of Wistar rats with experimentally induced brain injuries, using immunohistochemistry at the light microscopy level, demonstrated the presence of Tf-R in regenerated endothelial cells, reactive astrocytes and in other cells, probably macrophages. Although Tf-R were seen in proliferating cells, Tf-R were also observed in nonproliferating cells, many of them macrophages. The receptors perhaps bind transferrin in edema fluid and play an important role in lesion repair.

Malignant meningioma metastasizing through the cerebrospinal pathway

A case of malignant meningioma metastasizing through the cerebrospinal pathway is presented. The primary tumor was a parasagittal malignant meningioma invading into the brain. The tumor seeded to the cerebellopontine angle cistern and thoracic spine after multiple operations. Although this type of tumor borders the CSF, metastasis through the cerebrospinal pathway is rare, and only 18 such cases have been reported (2, 3, 10, 12).