S-phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine

One hundred fifty-four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S-phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR-labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1%, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Nonmalignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well-defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.     

The proliferative potential of human ependymomas measured by in situ bromodeoxyuridine labeling

Twelve patients with ependymomas received a 30- to 60-minute intravenous infusion of bromodeoxyuridine (BrdU), 150 to 200 mg/m2 at surgery, to label tumor cells in the DNA synthesis phase. Labeled cells were detected in excised tumor specimens by indirect immunoperoxidase staining using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the total number of cells scored) was calculated for each specimen. All four spinal cord ependymomas had a BrdU LI of less than 1%, which is consistent with our clinical experience that most such tumors grow slowly and have an excellent prognosis. Five of the eight intracranial ependymomas also had a low BrdU LI of approximately 1% or less, and three had a BrdU LI of 3.2%, 3.4%, and 4.8%. The latter three tumors, only one of which was diagnosed as a malignant ependymoma at the time of study, were either recurrent or recurred within 2 years after gross or subtotal removal. Cytologic analysis of cerebrospinal fluid (CSF) was performed in five cases; CSF seeding of tumor cells was found in only one patient, who had a malignant ependymoma. A high BrdU LI did not always correlate with CSF seeding. Measurement of the LI using BrdU and anti-BrdU monoclonal antibodies can provide more accurate information on the proliferative potential of individual tumors and may lead to a more rational grading system of ependymomas. The results of such studies do not always predict the potential for CSF seeding.     

No prediction of recurrence of meningiomas by PCNA and Ki-67 immunohistochemistry

Immunohistochemistry for the expression of the proliferation markersproliferating cell nuclear antigen (PCNA) and Ki-67 wasstudied in 16 non recurring meningiomas, 11 meningiomasrecurring as benign tumors, 6 recurring as atypicalmeningiomas and in 9 recurring as malignant meningiomas.Non recurring meningiomas were defined in this studyas tumors without recurrence at least 8 yearsafter surgery. In addition 16 benign recurrences, 14atypical- and 12 malignant meningiomas were studied. Ineach group great variation of labeling indices (LI)= per cent of tumor cells labeled wasobserved, especially of PCNA LIs. The non recurringmeningiomas displayed lower mean LI for PCNA andKi-67 than did the recurring meningiomas of allgroups but the differences were not statistically significant.The same pattern was seen when totally resectedtumors were studied alone. Benign-, atypical-, and malignantmeningiomas had labeling indices that were related tothe grade of malignancy. Only PCNA LIs ofatypical- and malignant meningiomas were statistically significantly higherthan PCNA LIs of non recurring meningiomas. Thestudy indicates that PCNA and Ki-67 are ofminor value as predictors of recurrence of benignmeningiomas.     

PCNA和Ki-67在脑膜瘤组织中的表达及其意义

目的：探讨增殖细胞抗原（PCNA）和Ki-67核抗原在脑膜瘤中的表达及其与肿瘤良、恶性及复发的关系。方法:采用LSAB法检测80例脑膜瘤组织中PCNA和Ki-67的表达。结果：恶性脑膜瘤PCNA标记指数（PCNALI）和Ki-67标记指数（Ki-67LI)明显高于良性脑膜瘤（P＜0．01）和非典型性脑膜瘤（P＜0．05），复发脑膜瘤PCNA LI显著高于未复发脑膜瘤（P＜0．01），复发脑膜瘤Ki-67LI也显著高于未复发脑膜瘤（P＜0．01），Ki-67表达与PCNA表达呈正相关。结论：脑膜瘤细胞标记指数可作为判断脑膜瘤良；恶性的客观指标之一，标记指数对预测脑膜瘤的复发有一定意义。     

Proliferative activity of early gastric cancer measured by in vitro and in vivo bromodeoxyuridine labeling

Forty seven patients with early gastric cancer received a 30-minute intravenous injection of bromodeoxyuridine (BrdU), 1000 mg each 1 hour before laparotomy, to label tumor cells in the S phase. In 13 of 47 patients, specimens obtained by endoscopic biopsy were cultured in vitro at 37 degrees C for 1 hour under three times the atmospheric pressure in a vial with 400 microM BrdU. Labeled cells were detected in the resected specimen and the cultured specimen by immunohistochemical staining procedure. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the 1000 tumor cells) was calculated for each specimen. All patients without lymph node metastasis had an in vivo BrdU LI of less than 12%. In contrast, 31% of patients with early gastric cancer with an in vivo BrdU LI greater than 12% had lymph node metastasis. There was a correlation between the in vivo and the in vitro LI. Therefore, the in vitro BrdU LI of specimens obtained by endoscopic biopsy may be a useful indicator of lymph node status in patients with individual early gastric cancers before operations. If the in vitro BrdU LI is less than 12% lymph node dissection may not be necessary.     

Histopathology and MIB-1 labeling index predicted recurrence of meningiomas: a proposal of diagnostic criteria for patients with atypical meningioma

BACKGROUND: Although various histopathologic features have been associated with aggressive behavior or recurrence of meningiomas, there is little agreement about which features are the most important and in what combination. The objective of this study was to formulate diagnostic criteria for atypical meningioma. METHODS: Eighty-three patients with meningiomas who underwent macroscopic total resection and had been followed until they developed recurrent disease or for at least 10 years were studied. Thirteen histopathologic parameters that related to recurrence of the tumor were evaluated in each patient. All possible combinations of histologic parameters that were related significantly to recurrence were used to formulate scoring models. The model that included the fewest parameters and that could distinguish tumor recurrence best within 10 years was chosen as the final model. RESULTS: The final model included three parameters: loss of architecture, mitoses > or= 1.5/mm2, and necrosis. Of the 52 tumors with a score < 2 (0 or 1 of the 3 parameters), all except 1 tumor did not recur within 10 years, and they were all considered benign meningiomas. Of the 31 tumors with a score > or = 2 (2 or 3 of the 3 parameters), 94% recurred within 10 years (76% recurred within 5 years), and they were considered atypical meningiomas. The estimated 5-year and 10-year recurrence rates for the benign meningiomas were 0.0% and 1.9%, respectively, for benign meningiomas and 71.0% and 93.5%, respectively, for atypical meningiomas (P < 0.001). The estimated 5-year and 10-year mortality rates also were significantly different (0.0% and 0.0% vs. 22.1% and 26.7%, respectively; P < 0.001). The MIB-1 labeling index (LI) for the entire group studied ranged from 0.4 to 33.5 (mean LI, 8.4). Fifty-two tumors with an LI of < 10 did not recur within 10 years. Of the 31 tumors with an LI > or = 10, 97% recurred (71% within 5 years). CONCLUSIONS: Histopathology and MIB-1 LI were able to predict clinical outcomes of patients with meningioma. The authors propose that atypical meningioma may be diagnosed when two of the following three criteria are present: loss of architecture, mitoses > or = 1.5/mm2, and necrosis.     

AR、PCNA表达与脑膜瘤临床病理因素的相关性研究

目的探讨雄激素受体(AR)在脑膜瘤组织中的表达及其与肿瘤增殖潜力的关系.方法采用免疫组化SABC法,检测AR、增殖细胞核抗原(PCNA)在39例脑膜瘤组织中的表达.结果51.3%(20/39)的脑膜瘤组织中AR呈不同程度的表达.良性、非典型性、恶性脑膜瘤中AR表达率分别为31.6%(6/19)、58.3%(7/12)、87.5%(7/8).恶性脑膜瘤中AR阳性细胞数显著高于非典型性和良性脑膜瘤(P＜0.05).恶性脑膜瘤平均PCNA标记指数(PCNA U)明显高于非典型性(P＜0.05)和良性脑膜瘤(P＜0.05).AR阳性脑膜瘤的PCNA U高于AR阴性脑膜瘤(P＜0.05),AR表达与PCNA的表达呈正相关.结论脑膜瘤AR表达与其病理级别有关,AR参与了肿瘤的生长和血管生成;检测脑膜瘤中AR表达可间接反映肿瘤的增殖潜力.     

Determination of proliferative activities in human brain tumor specimens: a comparison of three methods

Summary Proliferative activities were determined in 72 human brain tumors, including 20 metastatic carcinomas, 41 gliomas, 8 meningiomas and 3 hematological tumors. Immunocytochemical techniques included labeling with monoclonal antibody (mAb) to bromodeoxyuridine (BrdU) which identifies S phase cells after previous in vitro BrdU incubation and paraffin embedding of fixed tissue specimens, and with mAb Ki-67 which reacts, in frozen sections, with a nuclear antigen expressed by all proliferating cells. BrdU labeling index (LI), Ki-67 LI and mitotic index (MI) correlated well with histological malignancy. Among the three proliferation indices, Ki-67 LI and BrdU LI were highly significantly correlated. With the exception of hematological malignancies, hyperbaric oxygenation of in vitro BrdU labeling did not significantly increase BrdU LI or depth of BrdU penetration into tissue. This study indicates that in vitro BrdU labeling is a useful alternative to Ki-67 immunolabeling of human brain tumor specimens. By such determination of tumor proliferation, it might be possible to design a more adequate postoperative therapy tailored to patients individually.     

Antigen expression on recurrent meningioma cells

Introduction

Meningiomas are intracranial brain tumours that frequently recur. Recurrence rates up to 20% in 20 years for benign meningiomas, up to 80% for atypical meningiomas and up to 100% for malignant meningiomas, have been reported. The most important prognostic factors for meningioma recurrence are meningioma grade, meningioma invasiveness and radicality of neurosurgical resection. The aim of our study was to evaluate the differences in antigenic expression on the surface of meningioma cells between recurrent and non-recurrent meningiomas.

Methods

19 recurrent meningiomas and 35 non-recurrent meningiomas were compared regarding the expression of MIB-1 antigen, progesterone receptors, cathepsin B and cathepsin L, using immunohistochemistry.

Results

MIB-1 antigen expression was higher in the recurrent meningioma group (p=0.001). No difference in progesterone receptor status between recurrent and non-recurrent meningiomas was confirmed. Immunohistochemical intensity scores for cathepsin B (p= 0.007) and cathepsin L (p<0.001) were both higher in the recurrent than in the non-recurrent meningioma group.

Conslusions

MIB-1 antigen expression is higher in recurrent compared to non-recurrent meningiomas. There is no difference in expression of progesterone receptors between recurrent and non-recurrent meningiomas. Cathepsins B and L are expressed more in recurrent meningiomas.     

Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma

There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29–81) and median Karnofsky performance status (KPS) score 90 (range 60–100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted.     

Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine.

Fifty-seven patients with brain tumors (29 gliomas, 23 meningiomas, 5 miscellaneous) received infusions of intravenous iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) 1-5 hr apart shortly before tumor removal. Excised tumor specimens were stained sequentially for BUdR and IUdR. The percentage of BUdR-labelled cells was determined to establish the labelling index (LI), or S-phase fraction, and the ratio of cells labelled only with IUdR to cells labelled with BUdR or with BUdR and IUdR was determined to calculate the duration of S-phase (Ts) and the potential doubling time (Tp) of each tumor. The BUdR LIs varied from less than 1% to 20%, reflecting the malignancy of each tumor. Despite the difference in LIs, however, Ts was fairly uniform (mean +/- SD, 8.7 +/- 2.0 hr). Tp varied from 2 days to more than 1 month and correlated closely with the BUdR LIs (Tp = 23/LI0.93; r2 = 0.91). Double-labelling studies with IUdR and BUdR allow the S-phase fraction, Ts and Tp to be determined from a single biopsy specimen and thus provide more useful information on the growth characteristics of individual tumors than can be obtained by single-labelling studies with BUdR.     

Different responses of benign and atypical meningiomas to gamma-knife radiosurgery: report of two cases with immunohistochemical analysis

Recent reports have shown that gamma-knife radiosurgery provides a safe and effective strategy for the management of brain tumors. To evaluate the role of stereotactic radiosurgery in the management of meningiomas, we investigated the histopathology of two patients. The patients, a 37-year-old man and a 54-year-old woman, presented with visual field disturbance or headache. Imaging studies demonstrated intracranial meningiomas-tentorial and sphenoid ridge, respectively. Each patient undewent subtotal surgical resection (more than 90% in both patients), followed by gamma-knife radiosurgery of the remnant tumor marginal doses of 15 Gy. Pathological examination of the original tumors revealed a meningothelial meningioma and an atypical meningioma, respectively. Enlargement of the remnant tumors 4 months after radiosurgery resulted in total surgical resection in both patients. Thirteen months later, the patient with the atypical meningioma underwent a third operation for early recurrence of the tumor. Histopathology was investigated, and MIB-1, p53, and bcl-2 labeling indexes (LI) were analyzed immunohistochemically. Histopathologically, the specimens showed necrosis and intratumoral vessel obliteration after radiosurgery in both cases. However, more remnant tumor cells survived in the atypical meningioma. Immunohistochemically, increased wild-type p53, decreased bcl-2 expression, and decreased MIB-1 LI were observed in the benign meningioma. In the atypical meningioma, on the contrary, MIB-1 LI was decreased and mutant-type p53 and bcl-2 expression were unchanged. The specimen from the third operation revealed an anaplastic meningioma, and MIB-1 LI was markedly increased. These findings suggest that the efficacy of radiosurgery may differ between benign and atypical meningiomas.     

Different activation of mitogen-activated protein kinase and Akt signaling is associated with aggressive phenotype of human meningiomas.

PURPOSE: Activation of intracellular signaling cascades has been implicated in the growth control of benign meningiomas, but their role for meningioma progression and outcome is unknown. Here we determined the expression and function of proteins involved in mitogen-activated protein kinase (MAPK) and phosphinositol-3 kinase (PI3K)/Akt signaling in benign, atypical, and malignant meningiomas and studied their association with clinicopathologic data including meningioma recurrence. EXPERIMENTAL DESIGN: Expression of various MAPK and PI3K signaling proteins was determined in 70 primary meningiomas and, if present, in recurrent tumors by immunohistochemistry and Western blotting. The expression patterns in primary and recurrent tumors were related to clinical data. The effect of MAPK and PI3K pathway inhibition on cell proliferation and apoptosis was determined using a primary malignant meningioma cell culture. RESULTS: Atypical and malignant meningiomas showed higher levels of phospho-Akt compared with benign tumors, and their proliferation could be inhibited by PI3K blocking using wortmannin. PI3K inhibition did not induce apoptosis in malignant meningioma cells. In contrast, expression of phospho-Raf and phospho-MAPK was decreased in aggressive meningiomas compared with benign tumors, but MAPK inhibition by PD98059 resulted in tumor cell apoptosis and decreased proliferation. Reduced MAPK activation was associated with meningioma recurrence, and PI3K activation was associated with poor preclinical condition and brain invasion of malignant meningiomas. CONCLUSIONS: Both MAPK and PI3K/Akt pathways are activated at different levels in benign and malignant meningiomas. Activation of PI3K/Akt signaling contributes to the aggressive behavior of malignant meningiomas, whereas MAPK activation is involved in both proliferation and apoptosis of malignant meningiomas.     

Clinical evaluation of DNA index in human brain tumors

We evaluated the DNA index values in 28 brain-tumor patients showing DNA aneuploidy on the DNA histogram obtained by flow cytometry. In 17 cases among them, the DNA index values were compared to BUdR labeling indices (BUdR-LI). Average DNA indices of individual tumor types were 1.89 +- 0.10 (6 glioblastomas multiforme), 1.93 +- 0.05 (4 anaplastic astrocytomas), 1.68 +- 0.09 (3 malignant meningiomas), 1.24 +- 0.03 (7 meningiomas), 1.19 +- 0.05 (2 pituitary adenomas) and 1.86 +- 0.24 (6 metastatic brain tumors). Slow-growing tumors such as meningioma and pituitary adenoma, had lower values than malignant tumors, except a case of a metastatic brain tumor. All malignant meningiomas had higher DNA index values than the other meningiomas. No difference was observed between the DNA index values of glioblastomas multiforme and anaplastic astrocytomas. DNA index values were correlated with BUdR-LI values (p < 0.05), and seven cases with low DNA index values (1.13–1.31) had low BUdR-LI values of less than 1%. Others with high DNA index values of 1.44 or more had high BUdR-LI values of 3.5% or more. These results suggest that high DNA index values is related to tumor malignancy, and despite the presence of some disparities, many slow-growing brain tumor has low DNA index values.     

Proliferative Activity as Measured by MIB-1 Labeling Index and Long-term Outcome of Visual Pathway Astrocytomas in Children

Although most visual pathway tumors are low-grade gliomas their biologic behavior is highly unpredictable. In order to determine whether assessment of proliferative activity can assist in predicting tumor behavior, we studied the MIB-1 labeling indices (MIB-1 LIs) in surgical specimens and monitored tumor growth in 31 consecutive children operated on between 1978 and 1997. The MIB-1 LIs at diagnosis varied from 0–10.6% (mean±SD, 3.27±2.49%). Tumor progression occurred in 19 patients leading to death in seven, three of whom had neurofibromatosis type 1 (NF1). No association between MIB-1 LI at initial diagnosis and both progression free and overall survival was apparent. However, the MIB-1 LIs increased to 15.2% and 18% in two patients with NF1 who developed highly malignant gliomas 6 and 6.5 years after irradiation. In the remaining patients the MIB-1 LIs did not change significantly over time in a total of 17 repeat surgeries. Three patients with LIs of 6.8%, 10.6% and 8.8% are stable after 6, 4.5 and 3.5 years with partial resection, biopsy and subtotal resection, respectively, and no further therapy in the first two and chemotherapy in the latter. Three patients (10%) with LIs of 6.4%, 4.8% and 2.2% either presented with or developed leptomeningeal spread during follow-up. While MIB-1 LI does not appear to assist in clinical decision making patient numbers were too small to find out whether response to chemotherapy varies with proliferative potential.     

Relation of proliferative activity to survival in patients with gastric carcinoma

The prognostic significance of proliferative activity in 167 gastric carcinomas was studied by means of an in vitro labeling method with bromodeoxyuridine (BrdU), using specimens obtained by endoscopic biopsy, and the results were correlated with conventional prognostic factors. The BrdU labeling indicates (BrdU LI) varied from 2.1 to 45%. When the in vitro BrdU LI were plotted against in vivo BrdU LI, a significant correlation was found between in vitro and in vivo BrdU LI (P less than .01). These results show that the in vitro BrdU LI of specimens obtained by endoscopic biopsy indicate accurate proliferative activities of gastric cancers. The BrdU LI were closely correlated with nodal status, vessel invasion, and tumor size. With regard to the correlation of BrdU LI and prognosis, patients whose tumors had a high BrdU LI (BrdU greater than LI less than 10%). When the BrdU LI and all the pathologic findings were entered simultaneously into the regression model, nodal status, tumor size, serosal involvement, and BrdU LI emerged as independent prognostic parameters. The present studies demonstrated the usefulness of the in vitro BrdU-labeling method to estimate the malignancy of gastric cancer preoperatively, and this method may be useful in designing the operative procedure and multimodal therapy for individual patients.     

Prognostic Value of Proliferation Index and Expression of the RNA Component of Human Telomerase (hTR) in Papillary Meningiomas

Papillary meningioma is a rare subtype of meningioma that often behaves aggressively. In order to characterize factors that may influence this behavior, we chose to compare MIB-1 labeling index (LI) and telomerase RNA localization (hTR) in papillary meningiomas, meningiomas, and atypical meningiomas. LI is now often used to supplement histologic grade in the evaluation of these lesions. More recent studies indicate that increased expression of hTR is detected in many neoplastic cells, and may play an essential role in cell immortalization. The study group consisted of five papillary meningiomas (and a recurrence in one case), 11 conventional meningiomas, and eight atypical meningiomas. Conventional meningiomas showed either negative or 1+ hTR. Atypical meningiomas showed 1+ hTR. Papillary meningiomas showed the highest hTR (five of six, including recurrence, 2–3+ and one 1+). Generally, the LI was very low for conventional meningiomas (<2%). The LI of atypical meningiomas ranged from 3–19%, mean 12%, and from 5.5–17.5%, mean 11.75% for papillary meningiomas. LI differentiated between meningiomas, and papillary or atypical meningiomas. hTR further delineated papillary (moderate to high) from atypical meningiomas (low). The combined variable of LI and hTR expression could be a useful independent prognostic indicator in patients with papillary meningioma.     

Recurrence of meningiomas

BACKGROUND: Macroscopic total resection with removal of involved dura and bone does not always prevent the recurrence of meningioma of histologically benign subtype. Many causative factors have been investigated, although the mechanism of recurrence remains unclear. Vascular endothelial growth factor (VEGF) is a key factor in meningiomas neovascularization, and the authors investigated whether VEGF expression can predict the recurrence of histologically benign meningiomas after macroscopic total resection. METHODS: Fifty-four patients with supratentorial convexity meningiomas were investigated at least 3 years after surgery or until tumor recurrence to clarify risk factors for recurrence. Patients were restricted to Simpson Grade 1 resection only, and the authors excluded multiple meningiomas, neurofibromatosis, and atypical and anaplastic meningiomas. Correlation between recurrence and the following factors were statistically analyzed: age, gender, tumor volume, tumor shape, bone change, brain edema, vascular supply, histologic subtype, MIB-1 labeling index (LI), and VEGF expression. RESULTS: Of the 54 patients with meningioma, 34 were positive (24: +1; 10: +2) for VEGF, and 20 were negative. Six (11.1%) meningiomas recurred during the follow-up period. Multivariate analysis revealed that high levels of expression of VEGF constituted the most useful predictor of recurrence (P = 0.005), followed by high MIB-1 LI (P = 0.039). The other factors were not significant. The tumor recurrence, when it occurred, was within the brain and not durally based. CONCLUSIONS: The current results suggest that high levels of VEGF expression are significantly related to the recurrence of meningioma. VEGF secretion from microscopic residue remaining after surgery may induce neovascularization, which promotes the recurrence of meningioma.     

Proliferative activity of central neurocytoma: Measurement of tumor volume doubling time,MIB-1 staining index and bromodeoxyuridine labeling index

Central neurocytoma is considered to be a benign intracranial neoplasm, but little is known about the biological behavior of this type of tumor.Proliferative activity of central neurocytoma was measured in 10 cases using MIB-1 staining for Ki-67 antigen.The MIB-1 staining value varied from < 0.1% to 5.6%, to indicating that some of these tumors have proliferative potential similar to that of anaplastic astrocytoma or malignant meningioma. Thebromodeoxyuridine labeling index (BUdR LI, BrdU LI) was measured in 2 cases and the results correlated well with those of the MIB-1 analysis. Tumor volume doubling time (Td) measured in one case was 358 days which is similar to that of malignant meningioma.In one case, the MIB-1 value taken beforeand after 58 Gy of radiation treatment decreased markedly from 5.6%to 0.2%. The other 9 cases were also treated by radiation therapy (50—60 Gy) and no tumor recurrence was observed during follow-up periods ranging from 23 to 160 months. Another two patients with partially removed and 3 with subtotallyremoved tumors showing relatively high MIB-1 values might also have benefited from radiation therapy.     

Reverse seeding of recurrent intraspinal malignant meningioma

Meningiomas are common intracranial and intraspinal tumors and constitute 15-20% of all primary brain tumors. Ten to 15% of all meningiomas are considered malignant. The main treatment of meningiomas is surgical resection. Meningioma recurrence following surgery is frequent. However, it is not clear whether recurrent meningiomas, close or distant to the primary resection site, arise from incomplete resection, dissemination of tumor fragments or from independent tumor growth. We herein describe a 40-year-old woman with intraspinal malignant meningioma recurring each time upwards, i.e. apparently by reverse way of seeding, via cerebrospinal fluid.