Analysis of loss of heterozygosity for chromosome 10 in patients with malignant astrocytic tumors: correlation with patient age and survival

2001 ◽  
Vol 95 (4) ◽  
pp. 651-659 ◽  
Author(s):  
Kenji Tada ◽  
Shoji Shiraishi ◽  
Takanori Kamiryo ◽  
Hideo Nakamura ◽  
Hirofumi Hirano ◽  
...  

Object. The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. Methods. The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. Conclusions. In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

1994 ◽  
Vol 80 (5) ◽  
pp. 877-883 ◽  
Author(s):  
Isabelle Salmon ◽  
Olivier Dewitte ◽  
Jean-Lambert Pasteels ◽  
Jacqueline Flament-Durand ◽  
Jacques Brotchi ◽  
...  

✓ High-grade astrocytic tumors constitute the most serious as well as the most common group of primary brain tumors. Although several prognostic factors have been proposed, little is known about the prognostic value of deoxyribonucleic acid (DNA) ploidy in adult astrocytic tumors. In a series of 146 adult patients, aged 16 to 82 years, the individual prognostic values of six variables were studied, namely: tumor histopathological grade, treatment, patient age, extent of tumor, ploidy level, and DNA histogram type. Cox's proportional hazard model was then applied to the data to ascertain which factors might independently determine patient survival. Univariate analyses revealed that histopathological grade, age, and DNA histogram type were very powerful prognostic factors. The statistical significance of the influence of adjuvant radiotherapy and chemotherapy was at a borderline level, and the two remaining variables (tumor extent and ploidy level) had no prognostic relevance. Multivariate analyses showed that age, histopathological grade, and DNA histogram type were independent, statistically significant prognostic factors. A prognostic score was calculated from Cox's polynomial function in which those factors were introduced. The best score corresponded to a patient aged 16 years with a hypertriploid low-grade astrocytoma, while the worst score corresponded to a patient aged 82 years with a diploid high-grade astrocytoma. The worst score:best score ratio revealed a risk 71 times higher for a bad prognosis. It is concluded that patient age, histopathological grade, and DNA histogram type are very powerful prognostic factors for adult astrocytic tumors. A prognostic score including those factors could be used to characterize astrocytic tumor aggressiveness presurgically on fine-needle aspirates, and to monitor the patient's postsurgical evolution to define the appropriate therapy.


1994 ◽  
Vol 81 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Frederick F. Lang ◽  
Douglas C. Miller ◽  
Maxim Koslow ◽  
Elizabeth W. Newcomb

✓ To characterize some of the genetic events underlying the development of glioblastoma multiforme, the authors analyzed 65 astrocytic tumors (seven pilocytic astrocytomas, eight astrocytomas, 16 anaplastic astrocytomas, and 34 glioblastomas multiforme) for loss of heterozygosity for chromosome 17p, loss of heterozygosity for chromosomes 10p and 10q, amplification of the epidermal growth factor receptor (EGFR) gene, and amplification of the oncogenes N-myc, c-myc, and N-ras using Southern blot analysis. Alterations of the p53 gene (positive immunostaining for p53 protein in tumors with or without p53 gene mutations) in these 65 tumors were analyzed previously. None of the 65 tumors showed amplification or rearrangement of N-myc, c-myc, or N-ras oncogenes. The molecular analysis presented here demonstrates distinct variants of astrocytic tumors, with at least three genetic pathways leading to glioblastoma multiforme. One pathway was characterized by 43 astrocytomas with alterations in p53. Glioblastomas with p53 alterations may represent tumors that progress from lower-grade astrocytomas. This variant was more likely to show loss of chromosome 17p than tumors without p53 alterations (p < 0.04). Seventy-five percent of tumors with loss of one 17p allele demonstrated mutations in the p53 gene. Loss of chromosome 10 was associated with progression from anaplastic astrocytoma (13%) to glioblastoma (38%) (p < 0.04). Amplification of the EGFR gene was a rare (7%) but late event in tumor progression (p < 0.03). A second pathway was characterized by six astrocytomas without p53 alterations and may represent clinically de novo high-grade tumors. These tumors were more likely to show amplification of the EGFR gene (83%) than tumors with p53 alterations. Sixty percent of tumors with EGFR amplification also showed loss of chromosome 10; loss of chromosome 17p was infrequent in this variant. One or more alternative pathways were characterized by 16 astrocytomas without p53 alterations and with none of the genetic changes analyzed in this study. Glioblastomas are a heterogeneous group of tumors that may arise via multiple genetic pathways.


2003 ◽  
Vol 98 (4) ◽  
pp. 807-811 ◽  
Author(s):  
Anan Bedavanija ◽  
Jürgen Brieger ◽  
Hans-Anton Lehr ◽  
Jan Maurer ◽  
Wolf J. Mann

Object. Acoustic neuroma is the most frequent benign tumor of the cerebellopontine angle, and surgery is still the most common form of treatment. To gain better insight into the dysregulated mechanisms causing growth of acoustic neuroma, the authors studied the proliferative activity of 34 consecutive samples by analyzing immunohistochemical staining with Ki-67 and proliferating cell nuclear antigen (PCNA), and apoptosis based on the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling. Data from these analyses were correlated with clinical parameters (that is, tumor size, duration of symptoms, and patient age). Methods. Apoptotic cells were found in none of the tumors. Proliferation measured on staining with Ki-67 and PCNA correlated with tumor size, but not with patient age or duration of symptoms. The authors demonstrated that tumors 18 mm or smaller in diameter have lower proliferation indices and growth rates, compared with tumors larger than 18 mm with high proliferative indices and growth rates. Additionally, they observed that these more aggressive, larger tumors occur mostly in patients younger than 50 years of age. Conclusions. Patients with tumors larger than 18 mm in diameter and who are younger than 50 years of age sustain an enhanced risk for fast-growing tumors because of these lesions' enhanced proliferative activity. For these patients the authors recommend active therapy.


2002 ◽  
Vol 96 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Bryce Weir ◽  
Lew Disney ◽  
Theodore Karrison

Object. The authors explore the risk of rupture in aneurysms categorized by size. Methods. A computerized database of 945 patients with aneurysms treated between 1967 and 1987 was retrospectively established. All available clinical and radiological studies were abstracted. Because of the recent interest in the size of intracranial aneurysms in relation to their likelihood of rupture, the database was searched with respect to this parameter. In 390 patients representing 41% of all cases, aneurysms were measured by neuroradiologists at the time of diagnosis. In 78% of the 945 patients there was only one aneurysm, and of the 507 aneurysms that were measured, 60% were solitary. Of all patients, 86% had ruptured aneurysms. The average age of all patients was 47 years, and for those with ruptured aneurysms it was 46 years. Of the ruptured aneurysms, 77% were 10 mm or smaller, compared with 85% of the unruptured aneurysms. It was found that 40.3% of the ruptured aneurysms were on the anterior cerebral artery or anterior communicating artery, compared with 13% of the unruptured aneurysms. None of the cavernous internal carotid artery (ICA) aneurysms were ruptured and 65% of the ophthalmic artery (OphA) aneurysms were. Of the unruptured aneurysms, 15% were located in the cavernous ICA or the OphA. Of the ruptured aneurysms, 29% were on the middle cerebral artery, compared with 36% of the unruptured aneurysms. The mean size of ruptured and unruptured aneurysms showed no statistically significant increase with patient age, although the difference in size between the ruptured and unruptured aneurysms decreased with increasing age. The mean size of all ruptured aneurysms (10.8 mm) was significantly larger than the mean size of all unruptured aneurysms (7.8 mm, p < 0.001); the median sizes were 10 mm and 5 mm, respectively. The size of ruptured aneurysms in patients who died in the hospital was significantly larger than those in the patients who survived (12 mm compared with 9.9 mm, p = 0.004). Symptomatic unruptured aneurysms were significantly larger than incidental unruptured aneurysms (14.6 mm compared with 6.9 mm, p = 0.032), which were, in turn, larger than aneurysms that were unruptured and part of a multiple aneurysm constellation. Both ruptured and unruptured aneurysms were larger in male than in female patients, but not significantly. Conclusions. Site and patient age, as well as lesion size, may affect the chance of rupture.


1993 ◽  
Vol 79 (6) ◽  
pp. 845-852 ◽  
Author(s):  
Alain Pierre-Kahn ◽  
Jean-François Hirsch ◽  
Mathieu Vinchon ◽  
Christine Payan ◽  
Christian Sainte-Rose ◽  
...  

A study was made of 75 children treated between 1970 and 1990, with partial, subtotal, or total removal of three intrinsic and 72 exophytic or surface brain-stem tumors. In all cases, the goal of surgery was to remove as much tumor as possible. Extent of removal was defined according to data obtained from postoperative computerized tomography or magnetic resonance imaging, and was considered partial when only a small amount of tumor was removed, subtotal when a few cubic millimeters of tumor was left, and total when no residual tumor was seen on postoperative radiological investigations. An ultrasonic aspirator was used for the 43 most recent operations. Among tumor removals without the aspirator, 24 (75%) were partial, eight (25%) subtotal, and none total; with the use of the aspirator, the number of partial removals decreased to 44.5% while that of subtotal and total removals increased to 32% and 23.5%, respectively. There were 69 gliomas (92%) and 47 benign tumors (62.6%). Forty-nine patients were irradiated postoperatively, and 14 of the 23 patients whose benign tumors were removed totally or subtotally did not undergo irradiation. This study showed that: 1) the overall prognosis of patients with malignant tumors was poor and was not improved by surgery; 2) the survival rate of those with benign tumors was significantly (p < 0.01) lower after partial removal than after total or subtotal removal (52% and 94%, respectively, at 5 years); 3) comparison of means and proportions (Student's and chi-squared tests) between benign and malignant tumors showed a significant difference relating to patient age (p < 0.03), peritumoral hypodensity (p < 0.001), and preoperative duration of symptoms (p < 0.001); 4) stepwise logistic regression analysis confirmed that two of these three variables were related to malignancy: namely, patient age at surgery (p < 0.03) and presence of peritumoral hypodensity (p < 0.001); and 5) routine postoperative irradiation was contraindicated after total or subtotal removal of benign tumors.


2000 ◽  
Vol 93 (3) ◽  
pp. 410-420 ◽  
Author(s):  
Alois A. Obwegeser ◽  
Ryan J. Uitti ◽  
John A. Lucas ◽  
Robert J. Witte ◽  
Margaret F. Turk ◽  
...  

Object. The authors studied neuropsychological performance following microelectrode-guided posteroventral pallidotomy in patients with Parkinson's disease (PD) and evaluated correlations with presurgical and surgical factors.Methods. Neuropsychological changes 3 months (43 patients) and 12 months (27 patients) after microelectrode-guided pallidotomy for PD are reported in a series of 44 consecutive patients with the disease, who improved neurologically, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in both the “off” (p < 0.001) and best “on” (p < 0.001) states.Findings of the vocabulary subtest of the Wechsler Adult Intelligence Scale—Revised (p < 0.01), Letter Fluency (p < 0.001), Verbal Fluency for semantic categories (p < 0.001), and the Wisconsin Card Sorting Test (p < 0.01) showed a significant decline in neuropsychological performance in patients 3 months after undergoing left-sided pallidotomy. Impairment in the language domain (semantic fluency) persisted at the 12-month follow-up examination (p < 0.01). Visual memory improved after right-sided pallidotomies (p < 0.01 after 3 months), with a nonsignificant trend toward persistent improvement 1 year postsurgery (p < 0.02 after 12 months). Preoperative semantic fluency was influenced by patient age (p < 0.001) and by the width of the third ventricle (p < 0.05), as measured by magnetic resonance imaging.A regression model revealed that semantic fluency 3 months postoperatively was significantly affected by the baseline score (p < 0.001), side of surgery (p < 0.001), handedness (p < 0.01), and patient age (p < 0.05). However, postoperative lesion volume, lesion location, number of tracks, number of lesions, distance from anatomical landmarks, or UPDRS score did not significantly contribute to neuropsychological outcome.Conclusions. Neuropsychological changes in a cohort of patients with PD who underwent pallidotomy and experienced excellent clinical benefits and minimum postoperative complications, emphasize the importance of neuropsychological examinations and further investigation of predictive factors.


2001 ◽  
Vol 95 (6) ◽  
pp. 933-943 ◽  
Author(s):  
Benedicto O. Colli ◽  
Ossama Al-Mefty

Object. Chordomas are rare tumors that arise from the remnants of the notochord. Because of their deep location, local infiltrative nature, and involvement of surrounding bone, treatment of chordomas is a challenge. In this study the authors analyze the data and prognostic factors obtained during the follow-up period (range 1–150 months, median 38 months) in 53 patients with craniocervical junction chordomas and 10 patients with chondrosarcomas. Methods. Several surgical approaches were used, and some tumor excisions required staged procedures. Survival was calculated according the Kaplan—Meier method. Statistical analysis was performed using Fisher exact, log rank and Kruskal—Wallis tests. Radical/subtotal resection was achieved in 77.8% of the patients. The mortality rate during the follow-up period was 14.3%. In patients harboring chondrosarcoma better 5-year recurrence-free survival (RFS) rates were demonstrated than in those with chordoma (100% and 50.7%, respectively). Histological patterns (typical or chondroid chordomas) and patient age at onset of symptoms had no effect on the RFS rates. Radical/subtotal resections were associated with better RFS rates than partial resection. Adjuvant proton-beam therapy was shown to increase the RFS rates compared with conventional radiotherapy (90.9% and 19.4%, respectively, at 4 years posttreatment). Karyotypically abnormal tumors were associated with the worst RFS rates compared with karyotypically normal lesions (44.5% and 90.3%, respectively, at 3 years). Cases of cranial nerve palsy followed by those with cerebrospinal fluid leakages were the most frequent postoperative complications. Permanent postoperative neurological deficit was observed in 28.6% of the patients. Conclusions. A better prognosis was observed in patients with chondrosarcoma compared with those harboring chordoma. Histological pattern and patient age at symptom onset were not factors that influenced prognosis in cases of chordoma. Extensive resection and possibly adjuvant proton-beam therapy provided better prognoses for these patients.


2002 ◽  
Vol 97 (2) ◽  
pp. 326-336 ◽  
Author(s):  
Peter J. D. Andrews ◽  
Derek H. Sleeman ◽  
Patrick F. X. Statham ◽  
Andrew McQuatt ◽  
Vincent Corruble ◽  
...  

Object. Decision tree analysis highlights patient subgroups and critical values in variables assessed. Importantly, the results are visually informative and often present clear clinical interpretation about risk factors faced by patients in these subgroups. The aim of this prospective study was to compare results of logistic regression with those of decision tree analysis of an observational, head-injury data set, including a wide range of secondary insults and 12-month outcomes. Methods. One hundred twenty-four adult head-injured patients were studied during their stay in an intensive care unit by using a computerized data collection system. Verified values falling outside threshold limits were analyzed according to insult grade and duration with the aid of logistic regression. A decision tree was automatically produced from root node to target classes (Glasgow Outcome Scale [GOS] score). Among 69 patients, in whom eight insult categories could be assessed, outcome at 12 months was analyzed using logistic regression to determine the relative influence of patient age, admission Glasgow Coma Scale score, Injury Severity Score (ISS), pupillary response on admission, and insult duration. The most significant predictors of mortality in this patient set were duration of hypotensive, pyrexic, and hypoxemic insults. When good and poor outcomes were compared, hypotensive insults and pupillary response on admission were significant. Using decision tree analysis, the authors found that hypotension and low cerebral perfusion pressure (CPP) are the best predictors of death, with a 9.2% improvement in predictive accuracy (PA) over that obtained by simply predicting the largest outcome category as the outcome for each patient. Hypotension was a significant predictor of poor outcome (GOS Score 1–3). Low CPP, patient age, hypocarbia, and pupillary response were also good predictors of outcome (good/poor), with a 5.1% improvement in PA. In certain subgroups of patients pyrexia was a predictor of good outcome. Conclusions. Decision tree analysis confirmed some of the results of logistic regression and challenged others. This investigation shows that there is knowledge to be gained from analyzing observational data with the aid of decision tree analysis.


2003 ◽  
Vol 98 (2) ◽  
pp. 359-365 ◽  
Author(s):  
Yuichiro Tanaka ◽  
Kazuhiro Hongo ◽  
Tsuyoshi Tada ◽  
Keiichi Sakai ◽  
Yukinari Kakizawa ◽  
...  

Object. Surgical cure can be achieved in pituitary adenomas when they are completely removed. It is controversial whether postoperative radiation therapy should be given to prevent recurrence, and whether an early reoperation should be performed for residual adenomas, because we have little information about the natural history of postoperative residual adenomas. Methods. The residual tumor volume was serially measured in 40 nonfunctioning pituitary adenomas (NFPAs) and the tumor volume doubling time (TVDT) was calculated. Correlations between the patients' age, tumor volume, log TVDT, and MIB-1 index were examined. Other factors including the patient's sex, cavernous sinus (CS) invasion by the tumor, or presence of an intratumoral cyst were analyzed to assess their influence on the TVDT. Values are expressed as the means ± standard deviations. Thirty-eight adenomas increased in volume and two decreased during a follow-up period ranging from 4 to 141 months (mean 52.5 months). Exponentially linear tumor growth was observed in the 38 growing adenomas regardless of the residual tumor volume, with the TVDT ranging from 506 to 5378 days (mean 1836 days). The patients' age was 57.1 ± 15.7 years (range 15–79 years), the tumor volume at the beginning of the magnetic resonance imaging observation period was 2.5 ± 2.2 cm3 (range 0.07–14.5 cm3), and the MIB-1 index was 0.73 ± 0.68% (range 0.1–2.9%). There was a correlation between the log TVDT and patient age (R = 0.73), an inverse correlation between the log TVDT and MIB-1 index (r = −0.49), and an inverse correlation between the MIB-1 index and patient age (r = −0.61). A significant difference (p = 0.0001) was noted between the TVDT (1106 days) in the 19 patients younger than 61 years of age and the TVDT (2566 days) in the 19 patients who were 61 years of age or older. There was also a significant difference (p = 0.0002) between the age (50.8 ± 15.3 years) of the patients with rapidly growing tumors (TVDT < 1836 days, 24 patients) and the age (69.1 ± 7.6 years) of the patients with slowly growing tumors (TVDT > 1836 days, 14 patients). Other factors including the patients' sex, CS invasion, and intratumoral cyst formation did not affect the TVDT of residual NFPAs. Conclusions. The tumor growth rate of residual NFPAs is strongly influenced by the patient's age. The TVDT in elderly patients is much longer than that previously reported. Treatment strategies that take into consideration the natural history of residual adenomas should be established especially in the elderly population.


2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 49-52 ◽  
Author(s):  
Keisuke Maruyama ◽  
Masahiro Shin ◽  
Masao Tago ◽  
Hiroki Kurita ◽  
Shunsuke Kawamoto ◽  
...  

Object. The purpose of this study was to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of arteriovenous malformations (AVMs) involving the corpus callosum. Methods. Thirty-two patients aged from 7 to 65 years (median 25 years) with AVMs of the corpus callosum underwent GKS between 1990 and 2002. The maximum AVM diameter was more than 3 cm in 11 patients (34%). The AVM volume ranged from 0.1 to 19.1 cm3 (median 1.6 cm3). The median dose to the AVM margin was 20 Gy (range 17–28 Gy). Patients were followed for 1 to 12 years (median 9 years). The angiographically confirmed actuarial obliteration rate was 64% and 74% at 4 and 6 years, respectively. Younger patient age (p < 0.05) and lower radiosurgery-based grading score (calculated from the patient age and AVM volume; p < 0.01) were the significant factors affecting successful AVM obliteration. No patient suffered a hemorrhage after GKS, although 28 patients (88%) had a history of hemorrhage from their AVMs. Radiation-induced neurological deficit was observed only in one patient (3%) who had undergone previous radiotherapy (50 Gy). No patient experienced complications of occlusion or stenosis of the normal vascular structures adjacent to the AVM. Conclusions. Gamma knife surgery is a safe and effective treatment for selected patients with AVMs involving the corpus callosum, and it carries a low risk of damaging adjacent critical vascular structures. Even ruptured AVMs with relatively large diameter can be successfully treated, especially in younger patients, with minimal morbidity and a low risk of repeated hemorrhage.


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