Differential expression of cell adhesion molecules (CAM), neural CAM and epithelial cadherin in ependymomas and choroid plexus tumors

A series of frozen specimens of 18 ependymomas and 7 choroid plexus tumors were examined for their expression of cell adhesion molecules, such as neural cell adhesion molecule (NCAM), its polysialylated isoforms (PSA NCAM), and epithelial (E-) cadherin, and of intermediate filament proteins, such as glial fibrillary acidic protein (GFAP) and cytokeratin, using various monoclonal and polyclonal antibodies. Normal choroid plexus and ependyma were taken as controls. Anti-E-cadherin immunoreactivity was observed on the basolateral part of most adult choroid plexus and benign choroid plexus papilloma cells. However, a small number of atypical papillomas and carcinoma cells showed anti- E-cadherin immunoreactivity throughout their cell surface membrane. NCAM were not expressed by adult choroid plexus and benign papilloma cells. Only a few cells expressed NCAM and PSA NCAM in developing choroid plexus, atypical papillomas and carcinomas. Cytokeratin expression was always observed in choroid plexus and their tumors; GFAP expression was variable from case to case. In contrast, ependymal cells and their tumors never expressed E-cadherin but strongly expressed NCAM. PSA NCAM was found in ependymomas exhibiting anaplastic features. All ependymomas strongly expressed GFAP and a few demonstrated slight expression of cytokeratin. These data suggest that, besides GFAP and cytokeratin, NCAM and E-cadherin are of potential diagnostic value in distinguishing choroid plexus tumors from ependymomas. E-cadherin and NCAM may play a role in the functional organization of normal choroid plexus and ependyma, respectively. In particular, incomplete or irregular anti-E-cadherin expression in choroid plexus tumors and PSA NCAM immunoreativity in ependymomas and choroid plexus tumors correlates with the emergence of anaplastic histological features.     

Choroid plexus epithelium (normal and neoplastic) expresses synaptophysin. A potentially useful aid in differentiating carcinoma of the choroid plexus from metastatic papillary carcinomas

As an incidental finding in paraffin sections of brain tissue used as positive controls for synaptophysin immunostain, the cytoplasm of choroid plexus epithelium present was found to stain strongly positively for this substance. This was subsequently found to be the case in normal choroid plexuses in autopsy material from infancy to old age, as well as in epithelial cells of papillomas and carcinomas of the choroid plexus. The latter findings may prove useful in differentiating choroid plexus carcinomas from metastatic papillary carcinomas of extracerebral origin with the exception of neuroendocrine carcinomas of various sites that are usually positive for synaptophysin.     

Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.     

Immunohistochemical studies on human brain tumors using anti-Leu 7 monoclonal antibody in paraffin-embedded specimens

Summary Using the four-step peroxidase-antiper-oxidase (PAP) method, the presence of the antigen recognized with anti-Leu 7 monoclonal antibody was investigated in paraffin-embedded human brain tissue and tumors. The antigen was demonstrated in the myelin sheaths, oligodendrocytes, and some choroid plexus cells in normal brain and in oligodendrogliomas, some astrocytomas and choroid plexus papillomas. The technique can be used to identify hormal and neoplastic oligodendrocytes.     

Clinicopathologic correlations in epithelial choroid plexus neoplasms: a study of 52 cases

Summary Sixty-seven tumor specimens of epithelial choroid plexus neoplasms obtained by 60 biopsies and 7 autopsies from 52 patients were investigated. Diagnoses of the first operations were choroid plexus papilloma (PP; 32 cases), choroid plexus papilloma with histological atypies (atypical PP; 6 cases), and choroid plexus carcinoma (PC; 14 cases). Carcinoembryonic antigen was expressed by 2 of the 3 biopsies autoptically recognized as metastatic carcinomas and by 2 autopsy cases of PC, while it was absent in all biopsies of true choroid plexus tumors. Tumor cells positive for transthyretin (TTR, prealbumin), S-100 protein (S100), and glial fibrillary acidic protein (GFAP) were detected in 39, 46 and 13, respectively, of the 49 cases of true choroid plexus tumors. Fourth ventricle tumors expressed more S100 (number of positive tumor cells) than lateral ventricle tumors, PP more S100 and TTR than atypical PP/PC. Tumors from patients 20 years of age and older expressed more GFAP and TTR than tumors from younger patients. Of the 30 patients with complete follow-up 19 were alive 2 to 11 years after surgery, including 7 recurrencies. Eleven died from the tumor 4 months to 7 years after surgery. The following histopathologic features (in order of decreasing significance) were correlated with poor prognosis (recurrency or fatal outcome): less than 50% of the tumor cells heavily positive for S100, presence of mitoses, absence of TTR-positive cells, brain invasion by cell nests, absence of marked stromal edema, and presence of necrotic areas. Our results indicate that some histologic features correlate significantly with poor prognosis and that immunohistochemical results correlate with tumor localization, age, and malignancy.     

Focal ependymal differentiation in choroid plexus papillomas

Summary Choroid plexus papillomas are usually easily distinguishable from papillary ependymomas by their delicate fibrovascular stroma and their cytologic similarity to normal choroid plexus epithelium. Exceptionally, however, examples are met which give rise to diagnostic difficulty. We therefore tested 22 choroid plexus papillomas for the presence of glial fibrillary acidic (GFA) protein using the immunoperoxidase technique. Positivity for the protein was found focally in epithelial tumor cells in nine of the 22 papillomas. All were in adults ranging from 19–66 years of age. Eight of the nine tumors originated in the 4th ventricle or from one of its lateral recesses. In six papillomas showing GFA protein in the cells, intracellular fibrils were found in a small number of elongated epithelial cells with the PTAH and/or Masson trichrome stains; in all these six cases, the GFA protein-positive cells were considerably more numerous than cells containing fibrils. Normal choroid plexus epithelium lacks GFA protein, but pathologically altered ependymal cells are often GFA protein-positive. Our findings therefore suggest that focal divergent glial (presumably ependymal) differentiation may be expressed in neoplastic choroid plexus epithelium, consistent with the origin of this epithelium from primitive neuroepithelial (ventricular) cells.This work was supported in part by Research Grant CA-11689 from the National Cancer Institute, USPHS     

Immunocytochemical detection of insulin-like growth factor II (IGF-II) in choroid plexus papilloma: a possible marker for differential diagnosis

BACKGROUND: Insulin-like growth factor II (IGF-II) has been detected in the choroid plexus of animals by means of immunohistochemistry and in situ hybridization, and this factor is thought to play an important role in the central nervous system (CNS). Little is known, however, about the presence and localization of this substance in the choroid plexus and in choroid plexus papilloma in humans. MATERIALS AND METHODS: 5 normal choroid plexus and 10 choroid plexus papillomas were examined for IGF-II by immunocytochemistry. IGF-II was not detected in normal human choroid plexus, whereas it was found in choroid plexus papilloma. Furthermore, to assess the possibility that IGF-II could serve as an immunohistological marker of choroid plexus papilloma, we used the same technique to examine paraffin-embedded samples from various kinds of brain tumors. RESULTS AND CONCLUSION: Our results suggest that IGF-II may be a useful marker for choroid plexus papilloma in differential diagnosis.     

Immunohistochemical study of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) in choroid plexus papilloma.

Insulin-like growth factor-II (IGF-II), a mitogen for various kinds of cells, has been shown to be secreted from the choroid plexus in animals. Insulin-like growth factor binding protein-2 (IGFBP-2), one of the six carrier proteins for IGFs, is also thought to be released from the choroid plexus, bind to IGF-II in the cerebrospinal fluid (CSF) and modulate the action of this growth factor. Little is known about the expression and localization of these substances in human choroid plexus and choroid plexus papillomas. The present immunohistochemical study demonstrated all six choroid plexus papillomas were positive for IGF-II, whereas normal choroid plexuses were negative for IGF-II. On the other hand, IGFBP-2 was positive in the endothelium and vascular media in the normal choroid plexus, while it was weakly positive in four and negative in two out of six choroid plexus papillomas. These results suggest that the alterations in the IGF-II/IGFBP-2 axis might be involved in the tumorigenesis of choroid plexus papilloma.     

Immunohistochemical study of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) in choroid plexus papilloma

Abstract

Insulin-like growth factor-ll (IGF-II), a mitogen for various kinds of cells, has been shown to be secreted from the choroid plexus in animals. Insulin-like growth factor binding protein-2 (IGFBP-2), one of the six carrier proteins for IGFs, is also thought to be released from the choroid plexus, bind to IGF-II in the cerebrospinal fluid (CSF) and modulate the action of this growth factor. Little is known about the expression and localization of these substances in human choroid plexus and choroid plexus papillomas. The present immunohistochemical study demonstrated all six choroid plexus papillomas were positive for IGF-II, whereas normal choroid plexuses were negative for IGF-II. On the other hand, IGFBP-2 was positive in the endothelium and vascular media in the normal choroid plexus, while it was weakly positive in four and negative in two out of six choroid plexus papillomas. These results suggest that the alterations in the IGF-II/ IGFBP-2 axis might be involved in the tumorigenesis of choroid plexus papilloma. [Neurol Res 1999; 21: 339-344]     

Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa

Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid plexus papillomas, have been rarely described. In the present report, the cytogenetic investigation of an atypical choroid plexus papilloma occurring at the posterior fossa of a 16‐year‐old male is described. Comparative genome hybridization analysis demonstrated gains of genetic material from almost all chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and loss of chromosome Y. The presence of polyploid cells was confirmed by fluorescence in situ hybridization analysis with probes directed to centromeric regions. Furthermore, the microscopic analysis of cultures showed nuclear buds, nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the presence of complex chromosomal abnormalities. Previous cytogenetic studies on choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid karyotypes. To the best of our knowledge, this is the first report of polyploidy in choroid plexus papilloma of intermediate malignancy grade. Although the mechanisms beneath such genome duplication remain to be elucidated, the observed abnormal nuclear shapes indicate constant restructuring of the tumor's genome and deserves further investigation.     

Disseminated choroid plexus papillomas in adults: A case series and review of the literature

Choroid plexus papillomas (CPPs) are uncommon, usually intraventricular, low-grade tumors, accounting for less than 1% of all intracranial neoplasms and 2–4% of brain tumors in children. Dissemination of CPPs to multiple levels of the neuraxis has been seldom observed. Thus far, only 26 adult patients have been reported in the English language literature. With some exceptions, disseminated CPPs have been observed in adults and involved multiple sites along the cerebrospinal fluid pathways. Occasionally, intraparenchymal extension has been documented, and secondary involvement of the suprasellar region has been reported in only five patients. Postoperative treatment of CPPs has not been standardized. Most recommended therapies have been extrapolated from a series of atypical papillomas or carcinomas of the choroid plexus in children. We herein report a series of three patients of disseminated choroid plexus papillomas providing additional insights into this relatively rare entity.     

Stress and Glucocorticoids Increase Transthyretin Expression in Rat Choroid Plexus via Mineralocorticoid and Glucocorticoid Receptors

Transthyretin (TTR) is a carrier for thyroid hormones and retinol binding protein. Several mutated forms of TTR cause familial amyloidotic polyneuropathy, an inheritable lethal disease. On the other hand, wild-type TTR has a protective role against Alzheimer's disease. Despite its overall importance in normal animal physiology and in disease, few studies have focused on its regulation. An in silico analysis of the rat TTR gene revealed a glucocorticoid responsive element in the 3' region of the first intron. Thus, we hypothesised that TTR could be regulated by glucocorticoid hormones and investigated the regulation of TTR expression in response to hydrocortisone in a rat choroid plexus cell line (RCP) and in primary cultures of choroid plexus epithelial cells (CPEC). In addition, the effect of psychosocial stress on TTR expression was analysed in rat liver, choroid plexus (CP) and cerebrospinal fluid (CSF). In RCP and CPEC cultures hydrocortisone upregulated TTR expression, an effect suppressed by glucocorticoid receptor and mineralocorticoid receptor antagonists. Moreover, induction of psychosocial stress increased TTR expression in liver, CP and CSF of animals subjected to acute and chronic stress conditions. Overall, we conclude that stress upregulates TTR expression in CP.     

An immunohistochemical study of cytokeratin and glial fibrillary acidic protein in chroid plexus papilloma

Summary Cellular localization of cytokeratin and glial fibrillary acidic protein (GFAP) was examined in two normal choroid plexuses and five choroid plexus papillomas by the peroxidase-antiperoxidase (PAP) method and double immunofluorescence (IFL) microscopy. Cytokeratin was observed in the majority of epithelial cells in all samples of normal and neoplastic choroid plexuses. On the other hand, GFAP was observed in some of the constituent epithelial cells in two cases of papilloma. Most of these GFAP-positive papilloma cells were simultaneously positive for cytokeratin, as could be seen by the PAP stainings of serial sections and by the double IFL stainings of the same sections. From these findings, it was suggested that normal and neoplastic choroid plexus epithel cells usually express cytokeratin and that some of the neoplastic cells can simultaneously express boty cytokeratin and GFAP.     

Sellar-Suprasellar Extraventricular Choroid Plexus Papilloma : A Case Report and Review of the Literature

Choroid plexus papillomas (CPPs) are relatively rare neuroectodermal tumors that develop from choroid plexus epithelial cells and are usually restricted to the ventricles. Extraventricular CPPs are very unusual and can be difficult to diagnose and treat. A 50-year-old male patient was admitted to our clinic complaining of headache and visual deterioration. Neurological examination found no abnormalities except decreased light perception and secondary optic atrophy in the left eye. Endocrine testing revealed normal levels of hormones produced by the pituitary and target glands. Magnetic resonance imaging of the brain revealed a huge regular-shaped lesion in the sellar-suprasellar region occupying the sella turcica and extending into the suprasellar cistern and planum sphenoidale. The lesion was completely excised by microsurgery via an ordinary left-sided pterional approach. Histopathology identified the lesion as a choroid plexus papilloma. Following the case report, literature on the origin, differential diagnosis, and treatment of this rare tumor is reviewed.     

Bilateral cerebrovascular accidents in incontinentia pigmenti

Choroid plexus papillomas are rare tumors that are confined to areas in which the choroid plexus is normally located. In children, choroid plexus papillomas are predominantly located in the lateral ventricles. Clinically they present with signs of raised intracranial pressure, such as vomiting and increasing head size. Here we report on the clinical, radiologic, and histologic findings of a 4-year-old female who was found to have a tumor in the posterior fossa that had all the histologic hallmarks of a choroid plexus papilloma. This tumor did not originate from the roof of the fourth ventricle as expected but from the ependymal lining covering the median rostral medulla near the pontomedullary junction, a location that so far has not been reported.     

儿童脉络丛乳头状瘤

目的 总结儿童脉络丛乳头状瘤的临床特点和治疗经验。方法 回顾分析过去6年间我科收治的24例儿童脉络丛乳头状瘤的临床资料。结果 本组24例,占同期儿童颅内肿瘤的1.6％,发病平均年龄为7.7岁,男女之比为5:7。肿瘤位于侧脑室者14例;第四脑室内者7例;第三脑室内者2例;CPA 1例。显微手术全切和近全切除率达95.9％(23/24),术后复查CT的11例均有脑积水和/或硬膜下积液,经穿刺外引流和分流手术治愈。结论 儿童脉络丛乳头状瘤为良性肿瘤,预后较好,手术切除和及时处理术后并发症是治疗的关键。     

Congenital brain tumors: diagnostic pitfalls and therapeutic interventions

Congenital brain tumors are rare, accounting for 0.5% to 4% of all pediatric brain tumors. A 10-year retrospective study based on autopsy and neurosurgical clinical reports with a diagnosis of congenital/fetal/neonatal brain tumor identified 6 cases. Four cases were diagnosed antenatally by neuroradiology. Clinical outcomes in 5 cases resulted in death; 1 patient with choroid plexus papilloma underwent successful resection of the tumor and is still alive. Tumor pathologies consisted of 2 teratomas, 2 choroid plexus papillomas, 1 gemistocytic astrocytoma, and 1 glioblastoma multiforme. A literature review of all fetal cases specific to the pathologies presented in this series was also performed. Relative to the literature, this series contains a rare case of congenital gemistocytic astrocytoma. This series further sheds light on the diagnostic, histological, prognostic, and therapeutic differences between congenital brain tumors and tumors of the same pathology in older pediatric and adult populations.     

An immunocytochemical comparison of the glia-associated proteins glial fibrillary acidic protein (GFAP) and S-100 protein (S100P) in human brain tumors

Immunostaining patterns of two glia-associated proteins, glial fibrillary acidic protein (GFAP) and S-100 protein (S100P), were compared using the peroxidase-antiperoxidase (PAP) method on adjacent paraffin sections in 100 brain tumors including 52 astroglial tumors, 13 oligodendrogliomas, 14 ependymomas, 13 choroid plexus papillomas and 8 medulloblastomas. Most astroglial tumors showed similar immunoreactivity for both proteins. Fibrillary processes, however, showed a stronger and more crisp staining with anti-GFAP than with anti-S100P, whereas cell nuclei were labeled only for S100P. Focal dissociation of immunoreactivities for the two proteins was prominent in several malignant astroglial tumors including giant cell glioblastoma, and in subependymal giant cell astrocytoma. In oligodendrogliomas, GFAP-positive neoplastic oligodendrocytes also showed immunoreactivity for S100P; a smaller number of tumor cells were immunoreactive only for S100P, comparable to normal mature oligodendroglia. Most ependymomas were characterized by a similar distribution of cells immunoreactive for both proteins. In choroid plexus papilloma, absent or only focal immunoreactivity for GFAP contrasted with diffuse labeling for S100P in all cases; this seems of value for a differential diagnosis of papillary CNS tumors. In medulloblastoma, some tumor cells of a classical type were immunoreactive only for S100P; on the contrary, GFAP positive tumor cells with sparse or absent immunoreactivity for S100P were found in desmoplastic medulloblastomas. Similar immunoreactivities for both proteins in most tumors suggest a generally parallel production of both proteins by glial tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Constitutive expression of cyclooxygenase-2 (COX-2) in developing brain. A. Choroid plexus in human fetuses

It is believed that prostanoids produced by COX-1 activity are essential for the physiological functions of tissues while those produced by COX-2 lead to various pathological changes in these tissues. Brain is an exceptional organ where in some neurons COX-2 mRNA and its protein are constitutively expressed. Since some prostaglandins may play an important role in the control of blood-brain barrier and cerebral blood flow the purpose of the present study was to examine the COX-2 expression in choroid plexus, which participate in the nutrition of brain parenchyma of human fetuses. Study was performed on 25 brains of human fetuses from 12 to 38 weeks of gestation. In light and electron microscopy characteristic developmental transformation of choroid morphology was observed. In young fetuses from 12 to 20 week of gestation epithelial cells of choroid plexus are cuboidal, contain large amount of glycogen storage and their nuclei are COX-2 immunopositive. From 25 week of gestation until term the amount of glycogen in the choroid plexus diminishes, some apical nuclei are shifted toward central parts of the cells and number of cytoplasm organelles increases. In these cells expression of COX-2 protein is located in cytoplasm but epithelial nuclei are immunonegative. Our results provided evidence that COX-2 is constitutively expressed in the developing human choroid plexus. Different localization of COX-2 in choroid epithelial cells suggests that this enzyme may play a different role in various periods of the choroid plexus development.