Quantitative imaging of estrogen and progesterone receptors, estrogen-regulated protein, and growth fraction: immunocytochemical assays in 52 meningiomas

1994 ◽  
Vol 81 (5) ◽  
pp. 765-773 ◽  
Author(s):  
Pablo Bouillot ◽  
Jean-François Pellissier ◽  
Benedicte Devictor ◽  
Noel Graziani ◽  
Nicole Bianco ◽  
...  
Keyword(s):  
Histological Grade ◽  
Quantitative Imaging ◽  
Progesterone Receptors ◽  
Clinicopathological Features ◽  
Growth Fraction ◽  
Low Grade ◽  
Cell Nuclei ◽  
Content Type ◽  
Immunocytochemical Assay ◽  
Fine Print

✓ Quantitative imaging of estrogen receptors (ER's), progesterone receptors (PR's), estrogen-regulated protein (pS2), and growth fraction (Ki67) immunocytochemical assays were performed in 52 meningiomas. The results were correlated with clinical (age, sex, hormonal status, and tumor volume and location) and morphological (histological types and grades) data. The authors observed a lack of ER's in all meningiomas but the presence of PR's in 53% of these meningiomas. The immunoreactivity was restricted to tumor cell nuclei. The PR immunocytochemical assay was correlated with tumor location, histological type, histological grade, and pS2 immunocytochemical assay, but not with Ki67 immunocytochemical assay; high PR content was observed in cisternae, transitional, meningothelial, and low-grade meningiomas. Only 11 meningiomas showed more than 1% Ki67 immunoreactive nuclei. These meningiomas were usually located in the convexity and were of high histological grade. Estrogen-regulated protein immunoreactivity was observed in 34 meningiomas but the number of immunoreactive nuclei was low. The pS2 immunocytochemical assay was not related to clinicopathological features but was preferentially observed in PR-negative meningiomas. The results of this study are compared with those previously reported, and the function and regulation of PR's in meningiomas is discussed. The results indicate that 1) regulation of PR's and pS2 proteins in meningiomas differs from regulation in estrogen-dependent tissues such as breast or endometrium; 2) interruption of hormonal therapy in women presenting with a meningioma is not absolutely necessary; 3) meningiomas have different biological properties according to their clinicopathological features; and 4) future studies of hormonal clinical trials should be performed on well-defined meningioma subgroups.

Postoperative radiotherapy in the management of spinal cord ependymoma

1991 ◽  
Vol 74 (5) ◽  
pp. 720-728 ◽  
Author(s):  
Stephen J. Whitaker ◽  
Eric M. Bessell ◽  
Sue E. Ashley ◽  
H. J. G. Bloom ◽  
B. Anthony Bell ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Histological Grade ◽  
Postoperative Radiotherapy ◽  
Survival Rates ◽  
Cauda Equina ◽  
Low Grade ◽  
Content Type ◽  
Incomplete Surgery ◽  
Cause Specific Survival ◽  
Fine Print

✓ Fifty-eight patients with histologically verified spinal cord ependymomas were treated at the Royal Marsden Hospital and Atkinson Morley's Hospital between 1950 and 1987. The median age in this series was 40 years (range 1 to 79 years) and the male:female ratio was 1.8:1. Ten patients had tumors in the cervical cord and 10 in the thoracic cord; 14 tumors involved the conus medullaris and 24 the cauda equina. Forty ependymomas were grade 1 and 13 were grades II to IV (in five patients there was insufficient material for grading). Eleven patients underwent biopsy only, 33 had partial or subtotal resection, and 14 had complete resection. Forty-three patients received postoperative radiotherapy. The median follow-up period was 70 months (range 3 to 408 months). Cause-specific survival rates were 74% and 68% at 5 and 10 years, respectively. On univariate analysis, age, histological grade, postoperative neurological function, and era of treatment were significant prognostic factors for survival. The histological grade was the only significant independent prognostic factor. The relative risk of death from ependymoma was 9.0 for patients with tumor grades II to IV compared to grade I (p < 0.005, 95% confidence interval 2.7 to 30). The survival rates of patients following complete excision were significantly better compared to those after incomplete surgery (p < 0.025). The majority of completely resected neoplasms were low-grade cauda equina tumors. Despite incomplete surgery. 5- and 10-year progression-free survival rates following radical radiotherapy were both 59%, and cause-specific survival rates were 69% at 5 years and 62% at 10 years. This suggests that radiotherapy may achieve long-term tumor control in over half of those patients with residual spinal ependymoma.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 37-41 ◽  
Author(s):  
William F. Regine ◽  
Roy A. Patchell ◽  
James M. Strottmann ◽  
Ali Meigooni ◽  
Michael Sanders ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Content Type ◽  
Group B ◽  
Fine Print

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

The integration of metabolic imaging in stereotactic procedures including radiosurgery: a review

2002 ◽  
Vol 97 ◽  
pp. 542-550 ◽  
Author(s):  
Marc Levivier ◽  
David Wikler ◽  
Nicolas Massager ◽  
Philippe David ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Treatment Planning ◽  
Target Volume ◽  
Emission Tomography ◽  
Low Grade ◽  
Content Type ◽  
Positron Emission ◽  
Pet Scanning ◽  
Fine Print

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). Methods. Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography—guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

Estrogen and progesterone receptors in meningiomas

1984 ◽  
Vol 60 (5) ◽  
pp. 985-993 ◽  
Author(s):  
David W. Cahill ◽  
Nasir Bashirelahi ◽  
Louis W. Solomon ◽  
Thomas Dalton ◽  
Michael Salcman ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Gradient Centrifugation ◽  
Estrogen Therapy ◽  
Progesterone Receptors ◽  
The United States ◽  
Content Type ◽  
Therapeutic Implications ◽  
Exogenous Estrogen ◽  
French Group ◽  
Fine Print

✓ Two-thirds of all meningiomas and four-fifths of intraspinal and sphenoidal meningiomas occur in women. Meningiomas frequently enlarge or become symptomatic during pregnancy or during the luteal phase of the menstrual cycle. There is an increased incidence of meningiomas in women with breast carcinoma. In a series of 23 patients with meningiomas, the authors assayed biopsy specimens of the tumor for the presence of estrogen (ER) and progesterone (PR) receptors, using glycerol density gradient centrifugation and dextran-coated charcoal techniques. Significant levels of ER were found in only 17% of the patients, while significant PR levels were detected in 39%. Only one of the 16 tumors from female patients had significant ER levels, whereas three of the seven tumors from men had significant ER levels. Eight of the 16 tumors in women had significant PR levels, whereas only one of the seven tumors in men had a significant PR level. Thus, three out of four tumors with definite ER were from men, whereas eight of nine tumors with definite PR were from women. Of the eight women whose tumors contained PR, three were premenopausal and five postmenopausal. The single tumor with high levels of PR in the male patient was histologically atypical. The results of this series were compared with six published series of sex steroid assays in meningiomas. These seven series were divided into two groups: one group included two reports from the same laboratories in France, and the other the remaining five reports. Much higher percentages of both ER- and PR-positive tumors were reported from the French group. The authors suggest that this discrepancy may be due to the use of preoperative glucocorticoid therapy in the series from the United States. Since meningiomas are known to enlarge during periods when levels of circulating progestins are high, the presence of significant quantities of PR in a high percentage of tumors may have therapeutic implications for recurrent, malignant, or incompletely excised tumors, or for medically fragile patients. Conversely, since meningiomas are not known to enlarge during the proliferative phase of the menstrual cycle or with exogenous estrogen therapy, the small number of tumors positive for ER may indicate that ER lacks clinical significance. High levels of PR found in a small group of histologically aggressive tumors in several series may indicate that hormonal therapy may be especially useful in this difficult subset of patients.

Astrocytomas of the spinal cord in children and adolescents

1985 ◽  
Vol 63 (5) ◽  
pp. 669-675 ◽  
Author(s):  
Ronald Reimer ◽  
Burton M. Onofrio
Keyword(s):  
Spinal Cord ◽  
Histological Grade ◽  
Extended Period ◽  
Spinal Deformities ◽  
Duration Of Symptoms ◽  
Female Ratio ◽  
Content Type ◽  
Orthopedic Procedure ◽  
Male To Female ◽  
Fine Print

✓ The authors review 32 cases of spinal cord astrocytoma in patients under 20 years of age who were treated at the Mayo Clinic between 1955 and 1980. There was a 1.3:1 male to female ratio. Twenty patients were between 6 and 15 years of age at the time of diagnosis. The duration of symptoms prior to definitive diagnosis varied from 5 days to 9 years, with an average of 24 months. The most common symptoms were pain (62.5%), gait disturbance (43.7%), numbness (18.8%), and sphincteric dysfunction (18.8%). The most common neurological findings were a Babinski response (50.0%), posterior column sensory dysfunction (40.6%), and paraparesis (37.5%). A median follow-up period of 8.6 years (range 0.8 to 25.5 years) revealed that the survival time diminished with increased histological grade of the astrocytoma (p < 0.001). The development of postlaminectomy spinal deformities represented a serious postoperative complication. This occurred in 13 patients and was first recognized between 8 and 90 months postoperatively. Six deformities occurred following cervical laminectomy, and eight patients required at least one orthopedic procedure. It is crucial to follow these patients for an extended period of time to watch for postoperative spinal deformities.

Clot volume and clearance rate as independent predictors of vasospasm after aneurysmal subarachnoid hemorrhage

2004 ◽  
Vol 101 (2) ◽  
pp. 255-261 ◽  
Author(s):  
Christopher Reilly ◽  
Chris Amidei ◽  
Jocelyn Tolentino ◽  
Babak S. Jahromi ◽  
R. Loch Macdonald
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Clearance Rate ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Quantitative Imaging ◽  
Univariate Analysis ◽  
Ct Scans ◽  
Focal Neurological Deficit ◽  
Content Type ◽  
Fisher Grade ◽  
Fine Print

Object. This study was conducted for two purposes. The first was to determine whether a combination of measurements of subarachnoid clot volume, clearance rate, and density could improve prediction of which patients experience vasospasm. The second was to determine if each of these three measures could be used independently to predict vasospasm. Methods. Digital files of the cranial computerized tomography (CT) scans obtained in 75 consecutive patients admitted within 24 hours of subarachnoid hemorrhage (SAH) were analyzed in a blinded fashion by an observer who used quantitative imaging software to measure the volume of SAH and its density. Clot clearance rates were measured by quantifying SAH volume on subsequent CT scans. Vasospasm was defined as new onset of a focal neurological deficit or altered consciousness 5 to 12 days after SAH in the absence of other causes of deterioration, diagnosed with the aid of or exclusively by confirmatory transcranial Doppler ultrasonography and/or cerebral angiography. Univariate analysis showed that vasospasm was significantly associated with the SAH grade as classified on the Fisher scale, the initial clot volume, initial clot density, and percentage of clot cleared per day (p < 0.05). In multivariate analysis, initial clot volume and percentage of clot cleared per day were significant predictors of vasospasm (p < 0.05), whereas Fisher grade and initial clot density were not. Conclusions. Quantitative analysis of subarachnoid clot shows that vasospasm is best predicted by initial subarachnoid clot volume and the percentage of clot cleared per day.

Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful?

1995 ◽  
Vol 82 (3) ◽  
pp. 436-444 ◽  
Author(s):  
Peter A. Forsyth ◽  
Patrick J. Kelly ◽  
Terrence L. Cascino ◽  
Bernd W. Scheithauer ◽  
Edward G. Shaw ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Recurrence ◽  
Stereotactic Biopsy ◽  
Radiation Necrosis ◽  
Low Grade ◽  
Tumor Type ◽  
Content Type ◽  
Radiation Induced ◽  
Chondroblastic Osteosarcoma ◽  
Fine Print

✓ Fifty-one patients with supratentorial glioma treated with external beam radiotherapy (median dose 59.5 Gy) who then demonstrated clinical or radiographic evidence of disease progression underwent stereotactic biopsy to differentiate tumor recurrence from radiation necrosis. The original tumor histological type was diffuse or fibrillary astrocytoma in 21 patients (41%), oligodendroglioma in 13 (26%), and oligoastrocytoma in 17 (33%); 40 tumors (78%) were low-grade (Kernohan Grade 1 or 2). The median time to suspected disease progression was 28 months. Stereotactic biopsy showed tumor recurrence in 30 patients (59%), radiation necrosis in three (6%), and a mixture of both in 17 (33%); one patient (2%) had a parenchymal radiation-induced chondroblastic osteosarcoma. The tumor type at stereotactic biopsy was similar to the original tumor type and was astrocytoma in 24 patients (47%), oligodendroglioma in eight (16%), oligoastrocytoma in 16 (31%), unclassifiable in two (4%), and chondroblastic osteosarcoma in one patient (2%). At biopsy, however, only 19 tumors (37%) were low grade (Kernohan Grade 1 or 2). Subsequent surgery confirmed the stereotactic biopsy histological findings in eight patients. Follow-up examination showed 14 patients alive with a median survival of 1 year for the entire group. Median survival times after biopsy were 0.83 year for patients with tumor recurrence and 1.86 years for patients with both tumor recurrence and radionecrosis; these findings were significantly different (p = 0.008, log-rank test). No patient with radiation necrosis alone died. Other factors associated with reduced survival were a high proportion of residual tumor (p = 0.024), a low proportion of radionecrosis (p < 0.001), and a Kernohan Grade of × or 4 (p = 0.005). In conclusion, in patients with previously irradiated supratentorial gliomas in whom radionecrosis or tumor recurrence was clinically or radiographically suspected, results of stereotactic biopsy could be used to differentiate tumor recurrence, radiation necrosis, a mixture of both lesions, or radiation-induced neoplasm. In addition, biopsy results could predict survival rates.

Neurosurgical management of low-grade astrocytoma of the cerebral hemispheres

1984 ◽  
Vol 61 (4) ◽  
pp. 665-673 ◽  
Author(s):  
Edward R. Laws ◽  
William F. Taylor ◽  
Marvin B. Clifton ◽  
Haruo Okazaki
Keyword(s):  
Neurological Deficit ◽  
Important Variable ◽  
Surgical Removal ◽  
Low Grade ◽  
Survival Times ◽  
Duration Of Symptoms ◽  
Content Type ◽  
Long Duration ◽  
Fine Print

✓ The authors conducted a retrospective review of surgically treated, histologically proven cases of low-grade (Grade 1 or 2) astrocytomas. Follow-up analysis, with survival time as the end-point, was completed using multivariant statistical analysis. In the 461 cases of supratentorial low-grade astrocytoma in this study, age of the patient at the time of surgery was by far the most important variable in predicting length of survival. Other variables correlating with increasing survival times were: gross total surgical removal, lack of major preoperative neurological deficit, long duration of symptoms prior to surgery, seizures as a presenting symptom, lack of major postoperative neurological deficit, and surgery performed in recent decades. The multi-variant regression analysis showed that radiation therapy was of clear benefit, primarily in older patients with incompletely removed tumors. For purposes of establishing prognosis and testing the results, a “score” was developed to predict survival times, based on the most important variables. The data in this study provide a basis for the analysis of future modes of management of low-grade gliomas.

Hormonal dependency of cerebral meningiomas

1990 ◽  
Vol 73 (5) ◽  
pp. 743-749 ◽  
Author(s):  
Uwe M. H. Schrell ◽  
Eric F. Adams ◽  
Rudolf Fahlbusch ◽  
Robert Greb ◽  
Gustav Jirikowski ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Binding Sites ◽  
Solid Phase ◽  
Steroid Receptors ◽  
Progesterone Receptors ◽  
Nuclear Compartment ◽  
Content Type ◽  
High Affinity ◽  
Immunohistochemical Techniques ◽  
Fine Print

✓ Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas.

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 ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Loss Of Heterozygosity ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Chromosome 10 ◽  
Patient Age ◽  
Content Type ◽  
Unfavorable Prognostic Factor ◽  
Patient Âgé ◽  
Fine Print

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.

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