Significance of immunohistochemistry in neuro-oncology. I. Demonstration of glial fibrillary acid protein (GFAP) in extracranial metastases from primary brain tumors

8 cases were studied to determine whether immunohistochemical investigation with anti-GFAP could contribute to confirming a primary brain tumor origin for an extracranial metastasis. The materials studied consisted of 3 glioblastomas, 3 anaplastic astrocytomas, and 2 medulloblastomas, along with their extracranial metastases. GFAP could be immunohistochemically demonstrated in all 6 primary glial tumors as well as in the metastases of the 3 astrocytomas and of 2 glioblastomas. The medulloblastomas and their metastases were immunohistochemically GFAP-negative. GFAP is thus a marker for extracranial metastases of astrocytomas and glioblastomas. A negative result however does not exclude the possibility that a metastasis is of glial origin as shown by the GFAP-negative metastasis of the one glioblastoma.     

Expression of matrix metalloproteinases and their inhibitors in human brain tumors

Sixty human brain tumors, classified according to the New World Health Organization (WHO) classification including, grade I schwannomas, meningiomas and pilocytic astrocytomas, grade II astrocytomas, grade III anaplastic astrocytomas, grade IV glioblastomas, grade III anaplastic oligodendrogliomas and grade IV glioblastomas and lung and melanoma metastases were analyzed for the expression of three matrix metalloproteinases (MMPs), two tissue inhibitors of MMPs (TIMPs) and for MMP activity. Some correlation was found between MMP expression and the degree of malignancy. Western blotting analysis revealed a more uniform pattern of distribution of MMP-2 (gelatinase A) than of MMP-9 (gelatinase B) and MMP-12 (metalloelastase) among tumors. MMP-9 levels were found to be significantly higher in grade III anaplastic astrocytomas and anaplastic oligodendrogliomas than those in grade I schwannomas and meningiomas. Anaplastic astrocytomas and Grade IV glioblastomas expressed significantly higher levels MMP-12 than grade I meningiomas. All sixty tumors showed a similar pattern of activity in zymography, proMMP-9 being the major species detected. Interestingly, TIMP-1 and TIMP-2 expression levels were especially low in tumors of grade II and grade III but significantly higher in tumors of grade I, particularly in schwannomas. Taken together, these data suggest that: 1) a balance between MMPs and TIMPs has an important role to play in human brain tumors; 2) TIMP expression may be valuable markers for tumor malignancy. This revised version was published online in July 2006 with corrections to the Cover Date.     

Neurospecific proteins: potentials and prospects for their use in morphological research on tumors

Data on the application of neurospecific proteins S-100, GFAP, D2 glycoprotein and neuron-specific enolase (NSE) in the differential tumor diagnosis are reviewed. S-100 protein and GFAP are found in well differentiated astroglial tumors. S-100 protein can be used as melanoma and Schwannoma specific marker. In malignant CNS tumors there is a decrease of S-100 protein content up to its complete disappearance, while the content of GFAP is variable. D2 glycoprotein is detected in gliomas and medulloblastomas, being absent in other brain tumors. NSE is invariably present in apudomas and was also found in the majority of investigated astrocytomas, ependymomas, glioblastomas and in some medulloblastomas.     

Significance of immunohistochemistry for neuro-oncology. VI. Occurrence, localization and distribution of glial fibrillary acid protein (GFAP) in 820 tumors

In a retrospective study 820 tumors were immunohistochemically examined with anti-GFAP. All 224 astrocytomas and 105 of 112 glioblastomas were, at least focally, positive. 72% of ependymomas and 64% of oligodendrogliomas contained tumor cells which expressed GFAP. In such entities the reaction is dependent on the histologic subtype. Only 26 of 114 medulloblastomas (22.8%) demonstrated scattered GFAP positive cells. GFAP was also demonstrated in the CNS in gangliogliomas, monstrocellular sarcomas, 3 of 6 PNET, one non-classifiable tumor in a child, 1 plexus papilloma, in scattered stromal cells in 15 of 26 hemangioblastomas as well as in the mature glial component of intracranial germ cell tumors. Outside of the CNS there was evidence of GFAP in 3 cases with nasal glial heterotopy and in the myxoidal part of a pleomorphic salivary gland adenoma. Neoplasms which proved negative to GFAP in our series included purely neural differentiated tumors meningioma, neurolemmomas, chordomas, paragangliomas, sarcomas, lymphomas, melanomas and carcinoma metastases. Separating GFAP-positive reactive astrocytes from the actual tumor cells has proved to be a problem in the routine use of GFAP in differential diagnosis. Absence of an immunohistochemical response does not exclude a tumor of glial origin. Tissue samples which are too small, particularly in the case of anaplastic astrocytomas and glioblastomas can give false negative results.     

Routine immunohistochemical characterization of short term in vitro explants from human intracranial tumours.

35 intracranial tumours, 18 gliomas, 12 meningiomas, one neurilemmoma (neurinoma), one malignant melanoma and two metastases were successfully grown in-vitro and were submitted to immunocytochemical reactions, including cytokeratin, glial fibrillary acid protein (GFAP), vimentin, fibronectin, S-100 protein, neurofilament proteins, neuron-specific enolase (NSE) and basic myelin protein (MBP). Cytokeratin in metastases, GFAP and vimentin in gliomas, vimentin in meningiomas were consistently positive. S-100 protein was weakly and partially positive in gliomas, meningiomas, the neurilemmoma and malignant melanoma. Positive demonstration of fibronectin within cells was interpreted as a consequence of phagocytosis, except in meningiomas where fibronectin expression next to cell membranes seemed genuine. All other tested markers proved negative. The most important result seems to be that cells expressed markers irrespective of cellular shape and cytological morphology. It can be concluded that the cellular population as a whole consisted of tumour cells during the short time under observation and that supportive cell contamination during this early growth period was negligible.     

Expression of urokinase-type plasminogen activator receptor (uPAR) in primary central nervous system neoplasms.

The cellular receptor for urokinase-type plasminogen activator receptor (uPAR) is a member of the glycosylphosphatidylinositol (GPI) anchored protein family. It is a specific cell surface receptor for its ligand, urokinase-type plasminogen activator, which catalyzes the formation of plasmin from plasminogen to generate the proteolytic cascade and leads to the breakdown of the extracellular matrix. uPAR has been shown to correlate with a propensity to tumor invasion and metastasis in several types of non-central nervous system tumors. In this study, the authors examined the immunohistochemical expression of uPAR in 65 primary brain tumors (5 pilocytic astrocytomas, 5 diffuse astrocytomas, 6 anaplastic astrocytomas, 8 glioblastomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 6 anaplastic oligoastrocytomas, 4 gangliogliomas, 4 ependymomas, 5 medulloblastomas, 6 schwannomas, 5 meningiomas, 2 atypical meningiomas). The specimens were evaluated for intensity of immunostaining (0-3 scale), cellular localization of staining, and specific or unique patterns of staining. Some degree of uPAR expression was observed in all tumors. A significant positive correlation (P = 0.0006) between tumor grade and staining intensity was identified within the astrocytoma/glioblastoma subgroup, suggesting a possible correlation with anaplastic change and propensity to tumor invasion. Expression of uPAR in nonmalignant, noninvasive tumors such as schwannoma and meningioma suggests that uPAR may have other biologic functions in addition to promotion of tumor invasion.     

Importance of immunohistochemistry for neuro-oncology. III. Demonstration of glial fibrillary acidic proteins (GFAP) in anaplastic astrocytomas and glioblastomas

Expression of gliofibrillary acidic protein in 23 anaplastic astrocytomas and 33 glioblastomas has been investigated and correlated with tumor behavior as reflected in both the length of the preoperative history and in the post-operative survival time. Three degrees of positive immunoreactivity to anti-GFAP can be distinguished: positive GFAP reaction in more than 2/3 of cells; in 1/3 to 2/3 of all cells; in less than 1/3 of all cells; negative reaction. All anaplastic astrocytomas and 27 of 33 glioblastomas showed GFAP positive reactions. The proportion of highly reactive tumors is higher by anaplastic astrocytomas than by glioblastomas (7 of 33). For both astrocytomas and glioblastomas there is a tendency for a decrease in the expression of GFAP to be associated with a shorter preoperative history and with a shorter survival time. This is more prominent for astrocytomas than for glioblastomas. This finding supports the opinion expressed in previous publications that the GFAP expression is reversely related to the level of tumor anaplasticity.     

Nogo-A: a useful marker for the diagnosis of oligodendroglioma and for identifying 1p19q codeletion

The differential diagnosis between oligodendrogliomas and other gliomas remains a critical issue. The aim of this study is to verify the diagnostic value of Olig-2, Nogo-A, and synaptophysin and their role in identifying 1p19q codeletion. A total of 168 cases of brain tumors were studied: 24 oligodendrogliomas, 23 anaplastic oligodendrogliomas, 2 oligoastrocytomas, 2 anaplastic oligoastrocytomas, 30 glioblastoma multiforme, 2 diffuse astrocytomas, 4 anaplastic astrocytomas, 10 pilocytic astrocytomas, 9 ependymomas, 12 anaplastic ependymomas, 10 central neurocytomas, 10 meningiomas, 10 choroid plexus papillomas, 10 dysembryoplastic neuroepithelial tumors, and 10 metastases. All cases were immunostained with Olig-2, Nogo-A, and synaptophysin. In 79 cases, the status of 1p/19q had already been assessed by fluorescence in situ hybridization. Thus, in selected cases, fluorescence in situ hybridization was repeated in areas with numerous Nogo-A-positive neoplastic cells. Nogo-A was positive in 18 (75%) of 24 oligodendrogliomas, 8 (80%) of 10 dysembryoplastic neuroepithelial tumors, 6 (20%) of 30 glioblastoma multiforme, and 2 (20%) of 10 pilocytic astrocytomas. Olig-2 stained 22 (91.6%) of 24 oligodendrogliomas and all dysembryoplastic neuroepithelial tumors but also 24 (80%) of 30 glioblastoma multiforme and 8 (80%) of 10 pilocytic astrocytomas. Finally, synaptophysin stained 13 (54.1%) of 24 oligodendrogliomas, 3 (10%) of 30 glioblastoma multiforme, 1 (10%) of 10 pilocytic astrocytomas, and all neurocytomas. Among the 79 tested cases, original fluorescence in situ hybridization showed 1p/19q codeletion in 12 (52.2%) of 23 oligodendrogliomas, 8 (38%) of 21 anaplastic oligodendrogliomas, and 1 (4%) of 25 glioblastoma multiforme. However, after carrying out the Nogo-A-driven fluorescence in situ hybridization, 1p/19q codeletion was observed in 8 additional cases. Nogo-A is more useful and specific than Olig-2 in differentiating oligodendrogliomas from other gliomas. Furthermore, using a Nogo-A-driven fluorescence in situ hybridization analysis, it is possible to identify a larger number of 1p19q codeletions in gliomas.     

The determination of glial fibrillary acidic protein for the diagnosis and histogenetic study of central nervous system tumors: a study of 152 cases

Glial fibrillary acidic protein (GFAP) was purified from human spinal cord and cerebral white matter. GFAP was localized by an immuno-peroxidase method in normal adult and fetal human brains, rat brains, and 152 central nervous system (CNS) tumors. GFAP was found in reactive and normal astrocytes, immature cells of fetal brain at the 18th to 21st gestational weeks, and normal rat astrocytes. This GFAP staining was quite specific for glial tumors, including astrocytomas, glioblastomas, astroblastomas, and ependymomas. GFAP-positive cells were also found in oligodendrogliomas and choroid plexus papillomas, and they were interpreted as being astroglial or ependymal differentiations. Stromal cells in cerebellar hemangioblastomas were negative. However, engulfed astrocytes were found at the periphery of such tumors and often adjacent to the proliferate blood vessels. In meningiomas, neurinomas, metastatic carcinomas, pituitary adenomas and other non-glial tumors, GFAP-positive cells were not identified.     

神经系统多种肿瘤中组织型谷氨酰胺转氨酶蛋白的表达

目的 了解脑肿瘤中组织型谷氨酰胺转氨酶(tTG)蛋白的表达情况,探讨其与脑肿瘤类型和恶性程度的关系。方法采用免疫组织化学SP方法,检测tTG蛋白在62例星形细胞瘤、18例少突胶质细胞瘤、30例良性脑膜瘤、30例垂体腺瘤和10例正常脑组织中的表达。结果(1)脑肿瘤组织中tTG表达呈组织异质性,主要定位于血管内皮细胞、部分血管基底膜和部分肿瘤细胞胞质;(2)随着星形细胞瘤分化程度的降低,肿瘤细胞内tTG蛋白表达明显增加;(3)胶质瘤细胞内tTG蛋白表达强度明显高于良性脑膜瘤和垂体腺瘤;(4)在胶质母细胞瘤中,坏死和凋亡组织周围的肿瘤细胞tTG蛋白呈强阳性表达。结论脑肿瘤细胞内tTG蛋白表达与肿瘤的组织类型来源和恶性程度有关,可能促进星形细胞瘤恶性进展。     

Immunohistochemical profile of meningiomas and their histological subtypes.

Seventy-seven cases of meningioma (15 with single or multiple recurrences), selected on the basis of their histologic subtypes, and nine cases of neurilemoma were analyzed immunohistochemically for the presence of the five classes of intermediate filament proteins, neuron-specific enolase (NSE), protein S-100, epithelial membrane antigen (EMA), and HNK-1 (Leu-7). Most antibodies were studied with the alkaline phosphatase-antialkaline phosphatase method. The peroxidase-anti-peroxidase and avidin-biotin-complex methods were used for Leu-7 and NSE, respectively. Meningiomas were subdivided into groups showing cytokeratin or protein S-100 positivity. Coexpression of these two markers was rare (5%) and occurred in meningotheliomatous meningiomas only. Only in these cases was cytokeratin expression more frequent than in meningiomas taken together (33% versus 20%). In contrast, protein S-100 expression was less frequent (46% versus 60% on average). In fibrous meningiomas, both cytokeratins and NSE were expressed less frequently than on average (11% versus 20%, 67% versus 88%, respectively). Protein S-100 occurred in a higher percentage of cases. Transitional meningiomas did not show cytokeratin expression. Protein S-100 occurred in a higher percentage of cases. Transitional meningiomas did not show cytokeratin expression. Protein S-100 was expressed slightly more often than in the other subtypes. Psam-momatous meningiomas coexpressed more markers than any other subtype. Hemangioblastic and hemangiopericytic forms did not stain for EMA, but otherwise showed a staining profile similar to that of meningiomas. HNK-1 was expressed in 29% of meningiomas, particularly among tumors with anaplastic histologic features. There was no marker that retrospectively indicated impending recurrences.     

Factor VIII related antigen and glial fibrillary acidic protein immunoreactivity in the differential diagnosis of central nervous system hemangioblastomas

Nineteen hemangioblastomas, nine angioblastic meningiomas, ten metastases to the brain (including five renal cell carcinomas), and five primary renal cell carcinomas were studied using the immunoperoxidase method for Factor VIII related antigen and glial fibrillary acidic protein (GFAP). All tumor types showed Factor VIII immunoreactivity confined to endothelial cells. Factor VIII immunostaining revealed a distinct, though probably nondiagnostic, vascular pattern for hemangioblastomas as compared with metastatic carcinomas and angioblastic meningiomas. Most of the hemangioblastomas and metastases showed numerous GFAP-reactive cells with unequivocal astrocytic morphology primarily at the interface with brain parenchyma but also occasionally deep within the tumor. Within metastases these cells often were associated with penetrating fibrovascular septa. In a minority of hemangioblastomas and metastatic carcinomas there were rare GFAP immunoreactive cells that were indistinguishable from stromal or metastatic tumor cells, respectively. Angioblastic meningiomas showed no GFAP reactivity. It is concluded that the presence of GFAP-reactive cells alone is not helpful in differentiating between hemangioblastomas and intra-axial lesions. The lack of stromal cell immunoreactivity in angioblastic meningiomas and the rare staining of stromal cells in hemangioblastomas, seen also in central nervous system (CNS) metastases, suggest that except for the endothelial cells lining vessels, these primary CNS lesions are not antigenically closely related to either endothelial cells or astroglia. Furthermore, in the evaluation of tumors within the CNS, the significance of rare GFAP-positive tumor cells must be interpreted with caution.     

A simple method for the isolation of GFAP and its use for the study of brain tumors

A simple method is described in this paper for the production of a polyclonal antiserum against GFAP. The antiserum was tested on 212 primary brain tumours which had been selected from biopsy and autopsy material of the Institute of Pathological Anatomy at the Medical Academy of Erfurt, GDR. 52 of 81 astrocytomas (64%) and 26 of 47 glioblastomas (55%) gave GFAP-positive results. GFAP-negative responses were primarily recorded from tumours with severe anaplasia. GFAP was found in all 22 ependymomas tested. Epithelioid ependymomas, however, exhibited lower immunological reactions than tanycytic variants. Isomorphic oligodendrogliomas, meningiomas, medulloblastomas, and brain metastases of carcinomas were GFAP-negative. The possibility is discussed in some detail of falsely negative results on account of too little biopsy material or insufficient fixation of tumour tissue.     

Aberrant localization of the neuronal class III beta-tubulin in astrocytomas

BACKGROUND: The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of betaIII in neuronal/neuroblastic tumors is differentiation dependent. In contrast, the aberrant localization of this isotype in certain nonneuronal neoplasms, such as epithelial neuroendocrine lung tumors, is associated with anaplastic potential. OBJECTIVE: To test the generality of this observation, we investigated the immunoreactivity profile of betaIII in astrocytomas. DESIGN: Sixty archival, surgically excised astrocytomas (8 pilocytic astrocytomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO grade 2; 4 anaplastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade 4), were studied by immunohistochemistry using anti-betaIII monoclonal (TuJ1) and polyclonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1) was used as a marker for cell proliferation. Antibodies to glial fibrillary acidic protein (GFAP) and BM89 synaptic vesicle antigen/synaptophysin were used as glial and neuronal markers, respectively. RESULTS: The betaIII immunoreactivity was significantly greater in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas; median labeling index [MLI], 35%; interquartile range [IQR], 20%-47%) as compared with diffuse fibrillary astrocytomas (MLI, 4%; IQR, 0.2%-21%) (P <.0001) and was rarely detectable in pilocytic astrocytomas (MLI, 0%; IQR, 0%-0.5%) (P <.0001 vs high-grade astrocytomas; P <.01 vs diffuse fibrillary astrocytomas). A highly significant, grade-dependent relationship was observed between betaIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for betaIII (betaIII, P <.006; Ki-67, P <.0001). There was co-localization of betaIII and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected. CONCLUSIONS: In the context of astrocytic gliomas, betaIII immunoreactivity is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of betaIII-positive phenotypes in diffuse fibrillary astrocytomas with respect to prognostic and predictive value requires further evaluation. Under certain neoplastic conditions, betaIII expression is not neuron specific, calling for a cautious interpretation of betaIII-positive phenotypes in brain tumors.     

Expression of S-100 protein and glial fibrillary acidic protein in cultured submandibular gland epithelial cells and salivary gland tissues. Histogenetic implication for salivary gland tumors.

S-100 protein and glial fibrillary acidic protein (GFAP) were studied in human salivary gland tissues and human cultured submandibular gland epithelial cells. Immunohistochemically, ductal cells in normal salivary gland tissues were positive for S-100 protein and GFAP, but myoepithelial cells were uniformly negative. Immunocytochemically, cultured submandibular gland ductal cells were positive for S-100 protein and GFAP. By immunoblotting analysis of the cultured cell lysates, a 6.5-kd S-100 protein was detected. This band corresponded to S-100 protein purified from bovine brain. The cultured submandibular gland cells expressed 49- and 54-kd GFAP polypeptides. These results have important implications for the histogenesis of salivary gland tumors.     

An immunohistochemical and ultrastructural study of 243 gliomas with reference to the prognosis]

The localization of S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin as well as the relations between immunohistochemical reactions, grading and prognoses in 243 gliomas were investigated. In astrocytomas, both GFAP and S-100 protein were decreased along with the increase of tumor grades while the vimentin content was coincidently increased. The intensity of GFAP were negatively related to that of vimentin. Typical neoplastic oligodendroglial cells were known to be devoid of glial filaments and negative to GFAP and vimentin, anyhow, in the sporadic tumor cells, positive reaction to both GFAP and vimentin were identified, and these cells were considered to be either the astrocytes or the transitional cells between astrocytes and oligodendrocytes. Difference of the survival rates in cases with various gradings or intensities against S-100 protein and GFAP stainings were noticed. The results suggested that vimentin and GFAP may exist either independently or coexist synchronously in the astrocytomas as the markers, expressing the anaplasia stages of astrocytes. S-100 protein is considered to be an important indicator for both differentiation and prognosis of this tumor.     

Actin expression in neural crest cell-derived tumors including schwannomas, malignant peripheral nerve sheath tumors, neurofibromas and melanocytic tumors

Tumors that originate from neural crest-derived cells represent a heterogeneous group of neoplasms including benign and malignant tumors with melanocytic and schwannian differentiation. The immunophenotype of these tumors is well known but little is known about the expression of smooth muscle/myofibroblastic markers in these tumors. A total of 590 neural crest-derived tumors (50 benign schwannomas, five malignant peripheral nerve sheath tumors, 80 neurofibromas, 240 nevocytic nevi, 115 primary melanomas, and 100 melanoma metastases) were studied with respect to α-smooth muscle actin and muscle-specific actin expression. α-Smooth muscle actin and muscle-specific actin-positive tumor cells with a co-expression of S-100 protein were found in one benign schwannoma, one primary cutaneous melanoma, and four melanoma metastases. Four of these cases were examined ultrastructurally, but typical actin filaments with focal densities were not found in any of the four. Other immunohistochemical markers examined including desmin, h-caldesmon and smooth muscle myosin heavy chain were negative in the tumor cells. The present results suggest that neural crest-derived tumors could show expression of α-smooth muscle actin on rare occasion.     

Paragangliomas of the head and neck. Immunohistochemical analysis of 16 cases in comparison with neuro-endocrine carcinomas.

Sixteen cases of paragangliomas of the head and neck including 8 of the vagal body, 3 of the carotid body, 2 jugulotympanic, 2 vagal or jugulotympanic and 1 of the larynx were analysed. Clinically, 13 tumors were benign, 2 showed local aggressivity and 1 showed metastases. All tumors were tested with antisera directed against neuron-specific enolase (NSE), chromogranin A (CGA), S-100 protein, neurofilaments (NF), glial fibrillary acid protein (GFAP) and cytokeratin (CK). Immunohistochemical results were compared with those of 5 cases of neuroendocrine carcinoma (NC) (1 of the oral vestibule, 1 of the larynx, 1 Merkel-cell tumor of the skin and 2 medullary thyroid carcinomas). Immunoreactivity for NSE and/or CGA was always positive in all paragangliomas and NC. S-100 protein was positive in sustenticular cells in all cases of paragangliomas and focally in two cases of NC. NF and GFAP were focally positive in 3 and 2 paragangliomas respectively; and in 1 NC. CK was constantly negative in all cases of paraganglioma and constantly positive in all cases of NC. Antibody anti-CK is the single most useful immunomarker for differential diagnosis between paraganglioma, frequently benign neoplasms and NC commonly aggressive in the head and neck. These findings are consistent with the current concepts of the neuroendocrine system.     

Immunohistochemical expression of SPARC is correlated with recurrence,survival and malignant potential in meningiomas

Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki‐67 (MIB‐1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0–3) and intensity (0–3) of immunolabeling of the tumor cells. A high immunohistochemical score (4–6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB‐1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow‐up period of 47.53 ± 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB‐1 score were significantly higher in recurrent meningiomas than in non‐recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas.     

Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics

The histologic distinction between meningiomas and other tumors of the central nervous system occasionally can be difficult. Claudin-1 is a tight junction-associated protein recently shown to be expressed in anaplastic meningiomas. The purpose of this study was to determine whether immunohistochemical staining for claudin-1 could help distinguish meningiomas from histologic mimics, compared with commonly used markers. Tissue sections from 10 meningothelial meningiomas, 20 fibrous meningiomas, 10 atypical meningiomas, 7 solitary fibrous tumors of the meninges, 5 meningeal hemangiopericytomas, and 7 vestibular schwannomas were stained immunohistochemically for claudin-1, epithelial membrane antigen, S-100 protein, CD34, and glial fibrillary acidic protein. In total, 21 (53%) of 40 meningiomas were immunoreactive for claudin-1, whereas none of the other tumors were positive. In contrast, there was considerable overlap in the distribution of the other antibodies evaluated. Claudin-1 seems to be a specific marker for meningiomas in this context. Although its sensitivity is relatively low, claudin-1 may be helpful in a panel of immunostains to distinguish meningiomas from histologic mimics.