IMMUNOHISTOCHEMICAL DETECTION OF PROGESTERONE RECEPTORS AND THE CORRELATION WITH KI-67 LABELING INDICES IN PARAFFIN-EMBEDDED SECTIONS OF MENINGIOMAS

Female sex steroids may play a role in the proliferation of meningiomas, which usually have a high level of progesterone receptors (PgRs). We aimed to investigate the presence of PgRs and the Ki-67 labeling index (Ki-67 LI) in meningioma cases (N = 110) in relation to the severity of the disease. We studied PgR immunoreactivities and the Ki-67 LI in paraffin-embedded sections from meningiomas. Immunodetection of PgRs was conducted with peroxidase-antiperoxidase complex. Im muno detection of Ki-67 antigen was achieved by streptavidin-biotin-peroxidase complex. Of 110 meningiomas, in 57 (52%) the immunostaining for PgRs was moderately to strongly positive (Group 1), in 23 (20%) weakly positive (Group 2), and in 30 (28%) negative (Group 3). The positive immunostaining rate for the PgR in the benign meningiomas (76%) was significantly higher than that in nonbenign tumors. The positive immunostaining rate for the PgR was significantly higher in women (81%) than men (55%). The results suggested that progesterone may play a role in the growth of meningiomas. Our results confirmed that the immunodetection of the PgR and Ki-67 antigens on the paraffin sections of meningiomas provides a valuable tool for estimating the biological behavior of meningiomas.     

In situ analysis of cell kinetics in human brain tumors

Summary A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the same tumors with monoclonal antibody Ki-67 which identifies all proliferating cells, i.e., the growth fraction. LIs were counted in at least five different areas with high density of labeled cells; at least 1,000 cells were counted. In 13 metastatic tumors, Ki-67 LI was 8.3%–62.6%, and BrdU LI was 5.1%–28.0%. In 18 gliomas, Ki-67 LI was 1.4%–19.3%, and BrdU LI was 0.2%–11.6%. In 7 meningiomas, Ki-67 LI was 0.3%–3.0%, and BrdU LI was 0%–2.0%. Statistical comparison of Ki-67 and BrdU LIs by linear regression analysis revealed a highly significant correlation: BrdU LI=0.99+0.34 Ki-67 LI (r=0.92,P<0.001). A significant heterogeneity of proliferation patterns may occur within one sample from area to area, as well as between different samples of the same tumor, especially in gliomas; thus, some subjective influence on LIs by arbitrary sampling and selection could occur in quantitative evaluation of in situ cell kinetics of human brain tumors. This study indicates that our in vitro BrdU-labeling method allows the in situ identification of S phase cells in excellently preserved fixed tumor tissue which is well suited for further histological examination. This method compares favorably with Ki-67 labeling of frozen sections and might emerge as a powerful new tool for the routine study of cell proliferation in surgical specimens of human brain tumors.Supported by funds from the Commission for Cancer Research of the Medical Faculty of the University of Vienna     

Spinal meningiomas: age-related features

Objectives

Spinal meningiomas mainly occur in old patients, with a remarkable female prevalence. This study investigates the different features between younger and older patients in an adult population (>18 years).

Materials and methods

A surgical series of 120 adult patients operated on for spinal meningiomas at the Neurosurgical Clinic of the “Federico II” University of Naples is reviewed.In this series 117 patients with a sporadic spinal meningioma were divided in two groups: group I including 30 patients (25.6%) younger than 50 years of age, group II including 87 patients (74.4%) older than 50 years. 3 patients had a spinal meningioma and neurofibromatosis.Several parameters, including sex, predisposing factors, tumor location and growth, histology, recurrences, proliferation index Ki-67 LI, and outcome, are considered and compared in the two age groups.

Results

Group I showed an incidence of high cervical spine (C1-C4) meningiomas higher than group II (23.3% vs 3.4%, p = 0.026) and lower rate of thoracic tumors (60% vs 82.7%, p = 0.04). No significant differences of histological type and Ki-67 LI were found. Group I had 2 cases of atypical meningiomas (6.6% vs 0%, ns). Recurrences occurred in 6.6% of group I and 2.6% of group II, with no significance. In recurrent meningiomas values of Ki-67 LI were significantly higher than values in not recurrent meningiomas (p = 0.0001), whereas no difference of estrogen and progesterone receptor expression was noted.

Conclusions

Younger adult patients with spinal meningiomas show not rare occurrence of NF (9%) and significantly higher incidence of high cervical and lower incidence of thoracic localizations with respect to the older patients. On the other hand, there are not significant differences of histology, Ki-67 LI and recurrence rate, excepting for a slight difference for atypical meningiomas.     

Immunostaining for proliferating cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7–80.2% (mean 31.7%), in metastases 0–76.0% (mean 47.8%), and in meningiomas 0–53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P=0.0002) and BrdUrd LIs (P=0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-oberserver and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case. In some classic meningiomas, high PCNA scores do not reflect the proliferative activity of the tumor, as Ki-67 and BrdUrd LIs are very low in these cases. We conclude that PCNA immunolabeling is of limited value in the individual tumor, mainly due to overexpression in many tumors, and at present cannot be recommended to replace Ki-67 and/or BrdUrd labeling methods for routine determination of proliferative activity in human tumor specimens.Supported in part by a grant from the Oncology Commission, Medical Faculty, University of Vienna     

脑肿瘤中P53蛋白的表达及Ki－67LI的相关性研究

利用突变型Ｐ５３蛋白的单抗及Ｋｉ－６７单抗对５０例冰冻标本进行检测，结果发现，脑肿瘤中突变型Ｐ５３蛋白的表达阳性率为４６％。低恶度胶质瘤、高恶度胶质瘤及转移癌中Ｐ５３蛋白表达的阳性率不同，分别为１８．２％、５３．８％及１００％。Ｐ５３蛋白表达阳性的肿瘤中高Ｋｉ－６７ＬＩ比例为７０％，其中位数及均数为１４．３％、２０．７６±１８．３（％），而无Ｐ５３蛋白表达的脑瘤中，ｋｉ－６７ＬＩ中位数及均数分别为１．３９及５．１９±９．０（％）。结果表明，突变型Ｐ５３蛋白的表达与脑肿瘤的组织类型，分化程度及细胞的增殖有关，而它的高表达又可能是肿瘤恶性表型或转移的标志之一。     

Ki-67 immunoreactivity in human central nervous system tumors: a study with MIB 1 monoclonal antibody on archival material

Paraffin-embedded surgical specimens from 136 primary human central nervous system (CNS) tumors, including 50 meningiomas, 24 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 8 oligoden-drogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained, following microwave processing, using a streptavidin/peroxidase method and the MIB 1 monoclonal antibody (mAb) against the Ki-67 antigen. The following mean Ki-67 labeling index (LI) values ± SD were found: meningiomas, 2.47 ± 1.83; astrocytomas, 2.03 ± 2.03; anaplastic astrocytomas, 12.80 ± 6.29; glioblastomas, 14.57 ± 6.77; oligodendrogliomas, 5.06 ± 4.78; ependymomas, 2.63 ± 2.58; anaplastic ependymoma, 6.89; subependymomas, 1.79 ± 1.54; medulloblastomas, 18.77 ± 9.65; and paragangliomas, 2.19 ± 2.51. Our findings indicate that while malignant CNS tumors always exhibited high Ki-67 LI values, and benign CNS tumors generally displayed lower values, increased immunoreactivity for Ki-67 epitopes (Ki-67 LI higher than 4) was noted in a number of meningiomas, astrocytomas, ependymomas, oligodendrogliomas and paragangliomas, contrasting with their benign histological features. Further investigations of the Ki-67 immunoreactivity in CNS tumors and systematic correlation with the postoperative follow-up of patients are necessary to determine the value of Ki-67 LI in predicting the biological behavior of CNS neoplasms.Presented at the 69th Annual Meeting of the American Association of Neuropathologists, June 10–13, 1993, Salt Lake City, Utah, USA     

Automated nuclear segmentation in the determination of the Ki-67 labeling index in meningiomas

OBJECTIVE: Assessing the Ki-67 labeling index (LI) is laborious and time consuming. Therefore, an automated computer-based method was developed, which is able to identify and analyze immunolabeled and hematoxylin-stained nuclei in digital images of routine immunohistochemical slides. MATERIAL AND METHODS: The method is based on a plugin for the public domain image analysis software ImageJ, which runs on every operating system (free download at http://rsb.info.nih.gov/ij/). Percentage of Ki-67 immunostained nuclei were determined in 5 high power fields (x40) of immunostained slides (DAB detection technique, hematoxylin counterstain) of 20 Grade I, 20 Grade II, and 10 Grade III meningiomas conventionally by two independent investigators and automatically, respectively. The time effort was measured for each counting procedure. RESULTS: Enumerating conventionally or automatically did not reveal any significant differences in the mean labeling indices. Ki-67 LIs discriminated sufficiently between meningiomas of Grade I (median 1.7% Investigator 1 and 1.5% Investigator 2 vs. 1.5% automatically), Grade II (7.6%, 8% vs. 7.3%), and Grade III meningiomas (22%, 21% vs. 22%). The computer-based results correlated very closely with those obtained by manual counting (correlation coefficient = 0.98). The mean time effort for counting procedure per image was 374 s (130 s-435 s) for the conventional and 11 s (7 s-12 s) for the automated method. CONCLUSIONS: The described method can reliably assess the Ki-67 LI much faster than conventional enumerating. The computerized method has the advantages of objectivity, accuracy, repeatability, and ease of use. There is no request for special stains nor special image acquiring systems. The plugin can be downloaded at the "Morphometrie" section of http://www.uniklinikum-saarland.de/neuropathologie.     

Steroid receptors in meningiomas

Summary Meningiomas are more common in females and their course can be affected by changes in the hormonal milieu of the patient. Recently, a few studies have reported the presence of one or more steroid receptors in a small number of meningiomas. We have studied the estrogen and progesterone receptors (ER and PgR) of 11 surgically excised meningiomas. The receptors were assayed biochemically and localized at the cellular level using fluoroceinated estradiol and rhodamine-conjugated progesterone. Considerable amounts of ER were found in 4/11 cases, and PgR was high in 6/11 tumors. Cytoplasmic localization of the steroid binding sites was seen using both tracers. The presence of 10% of cells with two ++ intensity of the fluorescence correlated with tumors having positive ER values (>10 Fm/mg protein). The presence of nuclear fluorescence and the higher level of PgR seen in some tumors indicate that the ER present is functioning. This study confirms the presence of steroid binding sites in meningiomas and suggests that there may be a role for hormonal manipulation in selected patients.     

Determination of Ki-67 labeling index in pituitary adenomas using MIB-1 monoclonal antibody.

Proliferative activity of 94 pituitary adenomas was assessed by the determination of the growth fraction, using MIB-1 monoclonal antibody in formalin fixed, paraffin embedded sections. This index was correlated with clinical and radiological evidence of invasiveness. The mean Ki-67 labeling index for all pituitary adenomas was 0.84% (range 0-17.45%). Hardy stage E tumours (1.44%) had a higher Ki-67 labeling index (LI) as compared with Hardy stage 0 tumours (0.36%). The difference in the Ki-67 labeling indices between invasive and non-invasive adenomas was not statistically significant. Hence, the Ki-67 labeling index is not a reliable indicator of invasiveness in pituitary adenomas.     

Nucleostemin和Ki-67在垂体腺瘤组织中的表达及其临床意义

目的 研究nucleostemin基因和Ki-67抗原在垂体腺瘤中的表达,分析nucleostemin基因在垂体腺瘤细胞增殖及肿瘤发生和发展中的作用. 方法 收集垂体腺瘤手术标本71例,采用半定量RT-PCR方法检测垂体腺瘤标本中nucleostemin mRNA的表达情况,采用免疫组化方法检测垂体腺瘤石蜡切片中Ki-67抗原的表达情况.同时收集相关临床资料. 结果 本组71例垂体腺瘤手术标本均有nucleostemin mRNA表达.非侵袭性垂体腺瘤和侵袭性垂体腺瘤中nucleostemin mRNA、Ki-67标记指数(Ki-67LI)表达差异有统计学意义(P＜0.05).复发组与未复发组中Ki-67LI表达差异有统计学意义(P＜0.05).Nucleostemin mRNA表达水平与Ki-67LI呈正相关关系(r=0.237,P＜0.05). 结论 Nucleostemin基因在人垂体腺瘤的侵袭性行为中发挥重要作用,其表达增高和Ki-67表达水平升高之间存在正相关,二者可以作为判断垂体腺瘤侵袭性和预测复发的有效临床检测指标.     

Proliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: A comparative study

Summary Proliferating cell nuclear antigen (PCNA) is a 36-kDa DNA polymerase- auxiliary protein which accumulates in the nucleus during S phase of the cell cycle. Immunohistochemical labeling indices (LI) of PCNA and Ki-67 were compared using an avidin-biotin complex method on frozen sections of 27 nervous system tumors, 3 normal cerebral cortices, and 3 peripheral nerves. In glial tumors, PCNA and Ki-67 LI increased with increasing tumor grade (Daumas-Duport system). In 5 low-grade glial tumors, PCNA and Ki-67 LI were 1%, except for one optic nerve glioma (Ki-67 LI=6%). In 7 grade 3 astrocytomas, and 1 mixed glioma, PCNA LI were 1–1.5%, while Ki-67 LI were 2%–10%. In 7 grade 4 astrocytomas and 1 metastatic carcinoma, PCNA LI ranged from 6%–15% while Ki-67 LI ranged from 17%–30%. In 5 of 6 schwannomas, focally high PCNA LI (4%–65%) were noted, despite low LI with Ki-67 (1.6%). Scattered normal schwann cell nuclei also stained with PCNA, but normal cerebral cortex did not. These data suggest that: (1) in higher-grade gliomas, PCNA may be a more specific S-phase marker, although a less sensitive proliferation marker, than Ki-67; (2) PCNA LI do not distinguish low-grade gliomas from grade 3 astrocytomas; (3) in schwannomas, PCNA may not reflect proliferative activity since it seems to react with an epitope present in normal schwann cells; and (4) the variable PCNA staining pattern introduces greater difficulties in cell counting than with Ki-67. These factors may limit the use of this anti-PCNA antibody in evaluating nervous system tumors.Supported in part by an American Cancer Society Career Development Award (ADT). Presented in part at the 66th meeting of the American Association of Neuropathologists, San Francisco, CA, June 14, 1990     

Loss of chromosome 22 and proliferative potential in ependymomas

Fluorescence in situ hybridisation (FISH) analysis using total chromosome 22 painting and locus specific 22q11.2 (bcr locus) probes was performed on sections from archival paraffin-embedded tumours obtained from 28 patients diagnosed with either ependymoma, WHO grade 11 (18 cases) or anaplastic ependymoma, WHO grade 111 (10 cases). The Ki-67 labelling index (LI) analysis was carried out in parallel to estimate the tumours' proliferative potential. Loss of chromosome 22 was revealed in eleven (39%) ependymomas, seven (39%) WHO grade II and four (40%) anaplastic variants. Concurrent cytogenetic analysis was performed on 11 tumours to confirm the loss of chromosome 22 in four cases; clones with a loss of chromosome 22, which was identified by FISH, were not detected by standard cytogenetics in two samples. The loss of chromosome 22 was restricted either to the tumours' site or to sex or age of the patients studied. The Ki-67 LI ranged from 0.1 to 32.0% (mean 4.3%). Low-grade tumours significantly showed a lower mean Ki-67 LI than those classified as anaplastic tumours (3.1% and 6.4%, respectively). Additionally, the mean Ki-67 LI for ependymomas with a loss of chromosome 22 was significantly lower than that for tumours with chromosome 22 disomy (1.6% and 6.0%, respectively, p = 0.05), indicating that loss of chromosome 22 may be associated with the subset of ependymomas characterised by low proliferative capacities.     

垂体腺瘤侵袭性与galectin-3蛋白表达及Ki-67标记指数的关系

目的探讨半乳糖凝集素-3（galectin-3）蛋白表达及Ki-67标记指数（Ki-67u）与垂体腺瘤侵袭性的关系。方法运用免疫组化sP法检测50例标本中galectin-3蛋白的表达及Ki-67LI,分析galectin-3蛋白的表达及Ki-67LI与垂体腺瘤侵袭性的内在关系。结果galectin-3蛋白表达局限于泌乳素（PRL）腺瘤、促肾上腺皮质激素（ACTH）腺瘤及部分多激素分泌型腺瘤,在其他类型垂体腺瘤中表达呈阴性;且即lectin-3在上述类型侵袭性腺瘤中的表达水平（galectin-3计分为3,264＋1．066）明显高于非侵袭性腺瘤（gaIectin-3计分为1．613±0．850）（P〈0．01）。Ki-67LI在侵袭性组和非侵袭性组分别为2．754±1．029和1．692±0：858,两组有显著性差异（P〈0．01）。在表达galectin-3蛋白的垂体腺瘤中其表达水平与Ki-67LI之间存在正相关性（r=0．916,P〈0．01）。结论在PRL、ACTH腺瘤及部分多激素分泌型腺瘤中,galectin-3蛋白的表达与Ki-67LI呈明显正相关性,同时检测二者可以作为评价此类型垂体腺瘤侵袭性的重要参考指标之一。     

Correlation between clinical characteristics and proliferative activity in patients with craniopharyngioma

OBJECTIVES: The aim of the study was to correlate the Ki-67 and cyclin A labelling index (LI) with clinical characteristics and risk of recurrence of craniopharyngiomas. METHODS: 47 consecutive patients were studied, 21 female and 26 male, aged 34.3 (2.8) years. Immunohistochemical analysis was performed on paraffin wax embedded material using monoclonal antibodies directed against the proliferation associated nuclear antigen Ki-67 and cyclin A. RESULTS: The median Ki-67 LI was 8.6% (interquartile range, 4.4%-14.0%). Ki-67 LI was significantly higher in tumours with a heavy inflammatory reaction and diabetes insipidus at presentation, whereas other clinical and histological features were not associated with the proliferation index. There was a strong linear correlation between Ki-67 LI and cyclin A LI (r = 0.77; p<0.0001); therefore, cyclin A LI showed the same clinical and histological relations described for Ki-67 LI. Recurrence of craniopharyngioma occurred in 13 of 46 patients (28.3%). The median Ki-67 LI in the 13 recurrent craniopharyngiomas (9.0%) was not significantly different from that of non-recurring tumours (7.9%). Cyclin A LI was also not associated with the risk of relapse. CONCLUSIONS: This study confirms the great variability of proliferative activity in craniopharyngiomas. Ki-67 and cyclin A LIs were associated with the presence of a heavy inflammatory reaction and diabetes insipidus, but did not correlate with the long term risk of tumour regrowth.     

Involvement of disregulated c-myc but not c-sis/PDGF in atypical and anaplastic meningiomas

We investigated the expression of c-myc and c-sis/PDGF mRNA and protein products in 20 cases of meningiomas of various grades: 10 benign, 5 atypical and 5 anaplastic meningiomas. All cases of atypical and anaplastic meningiomas were positive for c-myc protein and mRNA by immunohistochemistry and in situ hybridisation, respectively, while all 10 benign meningiomas were negative for c-myc immunostaining, with only one benign tumour positive for c-myc mRNA. Expression of PDGF-BB protein and c-sis mRNA were seen in more than 80% of the meningioma cases and was not restricted to the histological grades of meningiomas. Semiquantitative analysis showed that the frequency of c-myc immunopositive cells positively correlated with Ki-67 proliferative indices. Our findings suggest that c-myc, but not c-sis/PDGF, has some concern to the malignancy of meningiomas.     

Proliferative potential of meningiomas determined with the monoclonal antibody Ki-67

Summary In 30 meningiomas we investigated the proliferation rate of various subtypes with the monoclonal antibody Ki-67. Frozen sections were incubated with Ki-67 antibody using a modified Alkaline Phosphatase anti-Alkaline Phosphatase (APAAP)-technique and evaluation of proliferation rate was done by cell counting. Meningiomas of the meningiotheliomatous, fibrous and angioblastic subtype without atypical histological findings contained 1% or less proliferating cells. In recurent tumors, in transitional and in anaplastic meningiomas there is a marked increase of proliferating cells up to 20%. The distribution of marked cells varies in recurrent tumors and anaplastic meningiomas, and a focal proliferation of tumor cells was seen in meningiomas from transitional type. Immunohistological labelling of proliferating cells in meningiomas may allow a more precise prediction of the proliferation potential of each meningioma.     

Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas

Conventional histological evaluation and subclassification of childhood ependymomas poorly predict their biological behaviour. The Ki-67 labelling index (Ki-67 LI), a measure of growth fraction, correlates with the biological behaviour of several neoplasms, and this retrospective study tested the hypothesis that Ki-67 LI is a prognostic indicator in childhood posterior fossa ependymomas. Immunocytochemistry using an antibody to Ki-67 was undertaken on 5  μm sections of formalin-fixed, paraffin-embedded tissue from 74 cases of childhood (age <16  years.) posterior fossa ependymoma. A Ki-67 LI was established by counting the proportion of labelled nuclei in more than 1000 cells from several histological fields. Several clinical and histological variables (including Ki-67 LI) potentially associated with survival were entered into univariate and multivariate analyses using a Cox proportional hazards model. Variables that showed a significant and independent association with survival were Ki-67 LI ( P <0.002), whether total surgical resection had been achieved according to operation records ( P <0.03), and whether no adjuvant therapy had been given ( P <0.01). Age, sex, and the presence of necrosis or microvascular proliferation did not correlate with survival. In our defined population of patients with ependymomas, Ki-67 LI is a strong prognostic indicator. We recommend that Ki-67 LI is used in the histological evaluation of childhood posterior fossa ependymomas during trials of novel adjunctive therapies.     

A clinicopathological and immunohistochemical study of central nervous system hemangiopericytomas

Hemangiopericytomas (HPC) of the central nervous system (CNS) are uncommon dural-based tumors that mimic meningiomas clinically and radiologically. Because there are few reports about these tumors from India, we aimed to study the clinico-pathological and immunohistochemical features of CNS HPC. During 2000 to 2008 all 23 patients diagnosed with HPC of CNS at our Institution were reviewed in the study (11 males and 12 females, mean age of 46 years). Clinical, radiological and histopathological features were reviewed. There were 14 patients with grade II and nine with grade III tumors. Immunohistochemistry with antibodies to epithelial membrane antigen (EMA), vimentin, S-100, CD34 and Ki-67 was done on routinely processed, paraffin-embedded sections of 20 tumors. All patients were EMA and S-100 negative, and vimentin positive. CD34 was positive in only five out of 20 patients. The mean Ki-67 labeling index was 4.25% in grade II tumors and 7.8% in grade III tumors. We concluded that HPC are distinct from meningiomas in morphology, immunohistochemistry and biologic behavior, although they resemble each other clinically and radiologically, HPCs need to be differentiated from meningiomas.     

Peritumoral Brain Edema in Meningiomas : Correlation of Radiologic and Pathologic Features

Objective

The primary objective of this study was to perform a retrospective evaluation of the radiological and pathological features influencing the formation of peritumoral brain edema (PTBE) in meningiomas.

Methods

The magnetic resonance imaging (MRI) and pathology data for 86 patients with meningiomas, who underwent surgery at our institution between September 2003 and March 2009, were examined. We evaluated predictive factors related to peritumoral edema including gender, tumor volume, shape of tumor margin, presence of arachnoid plane, the signal intensity (SI) of the tumor in T2-weighted image (T2WI), the WHO histological classification (GI, GII/GIII) and the Ki-67 antigen labeling index (LI). The edema-tumor volume ratio was calculated as the edema index (EI) and was used to evaluate peritumoral edema.

Results

Gender (p=0.809) and pathological finding (p=0.084) were not statistically significantly associated with peritumoral edema by univariate analysis. Tumor volume was not correlated with the volume of peritumoral edema. By univariate analysis, three radiological features, and one pathological finding, were associated with PTBE of statistical significance: shape of tumor margin (p=0.001), presence of arachnoid plane (p=0.001), high SI of tumor in T2WI (p=0.001), and Ki-67 antigen LI (p=0.049). These results suggest that irregular tumor margins, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI can be important predictive factors that influence the formation of peritumoral edema in meningiomas. By multivariate analysis, only SI of the tumor in T2WI was statistically significantly associated with peritumoral edema.

Conclusion

Results of this study indicate that irregular tumor margin, hyperintensity in T2WI, absence of arachnoid plane on the MRI, and high Ki-67 LI may be important predictive factors influencing the formation of peritumoral edema in meningiomas.     

MIB-1(Ki-67) index and transforming growth factor-alpha (TGFα) immunoreactivity are significant prognostic predictors for meningiomas

Mitotic index >6, proliferating cell nuclear antigen (PCNA) index >5%, high tumour grade and absence of progesterone receptors (PR) are significant predictors for poor outcome in meningiomas. Since MIB-1 (Ki-67) is a more specific cell proliferation marker, and overexpression of TGF-alpha is also associated with tumour progression, we compared the prognostic significance of these factors with the other indices. Intracranial meningiomas from 21 men and 36 women (age 54.5±1.7, mean±sem) were classified as 24 benign, 24 atypical and nine malignant. Twenty-one of the 57 tumours recurred (mean interval to recurrence was 57.3±13.1 months). The mean follow-up period for patients without tumour recurrence was 81.9±8.7 months. MIB-1 labelling index (LI) was expressed as percentage of labelled nuclei to total tumour nuclei counted in the most densely labelled areas. Analysis of variance revealed significant differences between tumour grades for MIB-1 labelling indices (0.75±0.21 for benign, 3.2±0.57 for atypical, 6.04±1.48 for malignant; P≤0.0066), and between malignant and non-malignant meningiomas for TGFα staining scores (P≤0.029). MIB-1 LI also correlated with mitotic and PCNA indices (P≤0.0001), but not with age of the patients. Male patients had higher tumour MIB-1 LI than females (P≤0.0128). Univariate analysis indicated that MIB-1 LI>3%, TGFα score >4 (scoring scale 0–5), mitotic index >6, and negative PR status were significant factors for worse outcome. Higher MIB-1 LI, TGFα score and mitotic index as continuous variables were also significant negative predictors. With multivariate analysis, both MIB-1 LI and TGFα score remained significant factors when paired with all other variables: TGFα or MIB-1 LI, respectively, mitosis, PCNA, tumour grade, PR status, age, sex, postoperative radiation therapy. We conclude that MIB-1 LI and TGFα score are important independent prognostic indicators for patients with meningiomas.