Fas Engagement Increases Expression of Interleukin-6 in Human Glioma Cells

The aim of this investigation was recognition of the epithelial differentiation and proliferative activity of ependymomas in the spinal cord compared with astrocytomas in the spinal cord and ependymoma in the brain. We investigated histopathological and immunohistochemical examination in thirty-five cases, including eleven ependymomas, thirteen astrocytomas in the spinal region and eleven ependymomas in the intracranial region. An anti-epithelial membrane antigen antibody (EMA), and two types of anti-cytokeratin antibodies, CAM 5.2 (45 and 52kDa) and keratin (56 and 64kDa) were applied as epithelial markers. The proliferative potential of the tumors was investigated using the Ki-67 labeling index (LI, %). Histologically, perivascular pseudorosettes were seen in all of the spinal and intracranial ependymomas. There were few ependymal structures in the spinal ependymomas except in the myxopapillary type. Immunohistochemical study demonstrated that nine (82%) were immunoreactive for EMA, eight (73%) were immunoreactive for CAM 5.2 and three (27%) were immunoreactive for keratin in the spinal ependymomas. In the spinal astrocytomas, no tumors were immunoreactive for EMA or CAM 5.2. One of thirteen cases was immunoreactive for keratin. The Ki-67 LI of the spinal ependymomas was lower than that of the intracranial ependymoma (p < 0.01). Epithelial differentiation was found in the ependymomas, which may reflect the differences in histological and biological features between ependymomas and astrocytomas in the spinal cord. Regional differences in ependymomas may influence not only clinical features but also histo-pathological characteristics.     

Histological spectrum of ependymomas and correlation of p53 and Ki-67 expression with ependymoma grade and subtype

BACKGROUND: Clinical and histological criteria for ependymoma prognosis are well recognized. Recently few studies have been done based on Immunohistochemistry for prognostication of these tumours. In this study we have correlated the histological spectrum with immmunoexpression of p53 and Ki67 in these tumors. AIMS: To know the incidence of ependymomas; study their morphological spectrum and to evaluate expression of P53 and Ki 67 in different morphological subtypes. MATERIAL AND METHOD: A retrospective study was preformed on 70 ependymomas received in a period between 1994 and 2001. Entire tissue received was processed for routine paraffin embedded H&E stained sections. Immunocytochemistry was performed using antibodies to GFAP, EMA, Pancytokeratin and synaptophysin, to differentiate papillary ependymoma from choroid plexus papilloma; clear cell ependymoma from oligodendroglioma and central neurocytoma; ependymoblastoma from other embryonal tumours. p53 and Ki-67 immunohistochemistry was performed to correlate their expression with various tumour grades and subtypes. RESULTS: There were 3 cases (4.2%) of Grade I ependymoma (2 cases of myxopapillary ependymoma and 1 case of subependymoma); 57 cases (81.5%) of ependymoma grade II (43 of these were of classical variety, 11 of clear cell ependymoma, 2 of papillary and 1 case of cellular ependymoma). There were 9 cases (12.8%) of anaplastic ependymoma (one of these was a clear cell ependymoma and 1 case (1.5%) of ependymoblastoma CONCLUSION: p53 and Ki67 indices can be used in routine diagnostic laboratories to supplement the tumor grade on histology and more studies with follow up should be performed to analyse the prognosis of different subtypes. The expression of Ki 67 and p53 was significantly higher in anaplastic ependymomas. 4 out of 11 cases of clear cell ependymomas showed higher Ki 67 indices as compared to classical grade II ependymomas, thus further highlighting the importance of differentiating the various subtypes.     

A case of cervicomedullary junction tanycytic ependymoma associated with marked cyst formation

Tanycytic ependymomas are a subtype of ependymomas that were formally recognized as a new pathological entity in the latest World Health Organization (WHO) classification of 2000. They occur mostly in the spinal cord. Only a few reports have analyzed the proliferative potentials of these tumors; however, it has been reported that the MIB-1 labeling index of tanycytic ependymoma is lower than that of other subtypes of WHO grade II ependymomas. We report a rare case of cervicomedullary junction tanycytic ependymoma associated with marked cyst formation. A 62-year-old man had a history of progressive gait disturbance, diplopia, and swallowing disturbance over a one-month period prior to admission. Magnetic resonance imaging (MRI) showed a cystic mass with a mural nodule at the cervicomedullary junction with Gd-DTPA enhancement. Cyst-subarachnoid shunt was performed using a far lateral approach. After 6 years, however, the man was readmitted to the hospital because of reaccumulation of the cyst. Partial removal of a mural nodule and a cyst-subarachnoid shunt were performed simultaneously by a midline suboccipital approach. The pathological diagnosis was tanycytic ependymoma. Postoperatively, the patient recovered well and was discharged from the hospital without further treatment. Most of the tumor cells had small, round nuclei; pleomorphism was minimal. The cytoplasm was dilated. The tumor cells were positive for EMA and s-100, and negative for CD-34. GFAP was not determined due to difficulty caused by background glial processes. The MIB-1 labeling index was less than 1%. Ultrastructurally, the tumor cells had ependymal cell features, such as desmosomes and microvilli. Based on these findings, the pathological diagnosis was tanycytic ependymoma.     

Immunohistochemical Markers for Prognosis of Ependymal Neoplasms

Intracranial ependymomas are the third most common primary brain tumor in children. Although clinical and histological criteria for ependymoma prognosis are recognized, studies have reported contradictory results. Prognostic significance based on immunohistochemistry of ependymomas has been reported in a few studies. One-hundred and twelve patients with intracranial ependymomas were examined retrospectively for immuno-expression of various tumor-associated antigens and apoptosis. The results demonstrated significant preponderance of expression of the tenascin, vascular endothelial growth factor protein (VEGF), epidermal growth factor (EGFR) and p53 protein in high-grade tumors. Also high-grade ependymomas revealed more prominent labeling indices (LI) for proliferative marker Ki-S1 and apoptotic index (AI), and lower LI for cyclin-dependent kinase inhibitors p27/Kip1 and p14ARF. For low-grade ependymomas the progression-free survival time (PFS) was found to be significantly shorter for Ki-S1 LI>5%, and for tenascin, VEGF and EGFR positivity. For high-grade ependymomas PFS was found to be significantly reduced for p27 LI<20%, p14ARF LI<10%, for p53 positivity, and for AI<1%. The CART modeling process exhibited five final groups of ependymoma patients (1) low-grade and tenascin-negative; (2) low-grade and tenascin-positive; (3) high-grade and p53-negative with p14 LI>0%; (4) high-grade with combination of either p53 positivity and p14 LI>10% or p53 negativity and p14 LI<10%; (5) high-grade and p53-positive with p14 LI<10%. In summary, some immunohistochemical variables were found to be the strong predictors of ependymoma recurrence and they seem to be useful for assessing individual tumor prognosis in routinely processed biopsy specimens together with tumor grade. For histologically benign ependymomas immunohistochemical study should be focused on Ki-S1, tenascin, EGFR and VEGF evaluation, whereas p53 expression and number of p27, p14 and ISEL-positive nuclei will be of value in determining PFS from high-grade ependymomas.     

Cerebrospinal fluid cytology in patients with ependymoma

BACKGROUND.

Ependymoma cells are known to occasionally exfoliate into cerebrospinal fluid (CSF). However, the frequency of CSF involvement in patients with ependymoma is unclear, and to the authors' knowledge the cytomorphologic features of the tumor cells have not been described in detail to date. In this study, the CSF findings in patients with ependymal neoplasms are summarized and the cytomorphologic features of ependymoma, including its variants, are illustrated.

METHODS.

A search of the pathology databases of 2 medical centers was performed to identify all patients with a histologic diagnosis of ependymoma in whom CSF samples were examined. Slides from CSF samples originally reported as atypical, suspicious, or positive were reviewed and the cytomorphologic features assessed. Follow‐up included a review of the medical records and histologic correlation.

RESULTS.

In all, 177 patients with a diagnosis of ependymoma were identified. Of these, 48 had a total of 94 cytologic preparations of CSF. Positive, suspicious, atypical, negative, and nondiagnostic results were noted in 6.4%, 5.3%, 4.3%, 79.7%, and 4.3%, respectively, of the specimens. The detection rate of tumor cells in CSF was 6.7% in 15 adults and 21.2% in 33 children, with an overall rate of 16.7%. Of the 8 patients with positive and/or suspicious diagnoses, 5 ependymomas exhibited anaplastic features and 1 tumor was a myxopapillary ependymoma. The positive samples were usually hypercellular, with cohesive epithelioid cells; long cytoplasmic processes resembling bipolar tanycytes were observed in the tanycytic variant of ependymoma.

CONCLUSIONS.

Exfoliated cells from ependymomas are recognizable in CSF samples, especially in patients with myxopapillary tumors and tumors with anaplastic features. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy

Despite surgery and radiotherapy, as many as 50 % of children with ependymomas will suffer from tumor recurrences that will ultimately lead to death. Our group’s initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing. We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms’ Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable. Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas. Normal brain and ependyma were used for background staining controls. Negative staining was defined as no staining or staining equaling the background intensity in normal brain tissues. In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1. Only 3 of 19 cases were positive for two or fewer tumor-associated antigens (TAAs); 16 of 19 cases were positive for three or more TAAs. In the 13 adult cases, all 13 demonstrated positive staining for EphA2, IL-13Rα2, and Survivin. Only 2 of 13 cases (15 %) demonstrated positive staining for WT1. All adult specimens were positive for three or more TAAs. Some ependymomas showed patchy variability in intensity. Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting.     

Immunohistochemical study of the expression of S-100 protein,epithelial membrane antigen,cytokeratin and carcinoembryonic antigen in thyroid lesions

The diagnosis of papillary carcinoma of the thyroid is based on the two morphological features that best characterize this tumor, the papillae and the nuclear changes. However, both the architectural and cytological hallmarks may be encountered in other conditions such as multinodular goiter, Grave's disease, thyroiditis and hyperplastic areas of follicular neoplasms and thus produce problems in the histopathological interpretation. The distinction of these lesions from papillary carcinoma has important implications for clinical management. Thus the availability of supportive diagnostic evidence would be helpful. In the present study we compared the immunoreactivity for S-100 protein, epithelial membrane antigen (EMA), cytokeratin (Ck) and carcynoembryonic antigen (CEA) in different thyroid pathologies. We conclude that the strong expression of S-100 protein, in combination with EMA expression, is of value in identifying papillary neoplasia and distinguishing it from papillary hyperplasia.     

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.     

Epithelial profile of epithelioid sarcoma. An immunohistochemical analysis of eight cases

Eight cases of epithelioid sarcoma were examined immunohistochemically, in order to clarify the adjunct epithelial profile of the tumor and to ascertain the intermediate filaments contained in the tumor cells. All tissues showed a strongly positive immunoreactivity for epithelial membrane antigen (EMA) and tissue polypeptide antigen (TPA). In the case of carcinoembryonic antigen (CEA), one showed a strong reaction, whereas the others were variably less stained. Cytokeratins (45 kd and 54 kd) specific for simple epithelia, including coelomic epithelium, were regularly found in all cases; a small number of cells were positive for high molecular weight cytokeratin (57 kd) and none for 66 kd cytokeratin. Coexpression of both cytokeratin and vimentin was confirmed using fresh-frozen materials. Therefore, both microscopic and immunohistochemical evidence supports the hypothesis that epithelioid sarcoma masquerades as a carcinoma.     

Tanycytic ependymoma of the spinal cord with anaplastic cytological features

In a 43-year-old man, an intramedullary spinal cord tumor spreading from the level of the T2 to T5 vertebrae was subtotally resected. The tumor predominantly consisted of a fascicular proliferation of spindle cells having bland nuclei and bipolar, long cytoplasmic processes, and a few perivascular pseudo-rosettes were found. Although there were no true ependymal rosettes, intracytoplasmic dot-like immunoreactivity for epithelial membrane antigen (EMA) was found in a few cells. In some areas, a dense and diffuse proliferation of anaplastic, short-spindled cells having hyperchromatic nuclei and scant cytoplasm was noted, and the Ki-67 labeling index was remarkably higher (18.2%) in these areas. Neither microvascular proliferation nor necrosis was observed. In the boundary region, these two areas showed gradual transition from one to the other. The patient has remained free from recurrence for 10 months postoperatively. This is the first documentation of tanycytic ependymoma in which tumor cells showed anaplastic cytological features.     

脊髓髓内室管膜瘤的显微外科治疗——附173例临床总结

背景与目的：随着神经影像技术，显微外科技术和术中监测手段的发展，大多数脊髓髓内肿瘤的早期诊断和治疗已成为现实。本研究旨在探讨显微外科手术治疗脊髓室管膜瘤的经验。方法：回顾性研究北京天坛医院神经外科脊柱脊髓组从2000年1月至2005年4月经显微外科手术治疗的髓内室管膜瘤173例，并分析其预后影响因素。结果：肿瘤全切除163例（94．2％），近全切除8例（4．6％），大部分切除2例（1．2％），出院3-6个月门诊随访好转142例（76．3％），余随访不全。结论：积极的显微外科治疗，争取全切是髓内室管膜瘤治疗的最佳选择，术前神经功能状况、肿瘤的性质与部位、手术技巧与切除程度等都是影响预后的重要因素。     

Anaplastic ependymoma simulating glioblastoma in the cerebrum of an adult

A case of anaplastic ependymoma of the cerebral hemisphere in which the histopathological features closely simulated those of glioblastoma is reported. The patient was a 72-year-old woman with a large, well-demarcated tumor in the left temporal lobe. The tumor was totally extirpated, but recurred 18 months later, and the patient died after 4 months. The extirpated tumor was well circumscribed from the surrounding brain tissue and consisted of a sheet-like, dense proliferation of atypical, short spindle or polygonal cells. Extensive geographic necrosis with nuclear pseudopalisading was seen. Although perivascular pseudorosettes were observed in many areas, true ependymal rosettes were absent. Immunohistochemistry for glial fibrillary acidic protein and epithelial membrane antigen and ultrastructural study confirmed the ependymal nature of tumor cells. The histopathological spectrum of anaplastic ependymoma is very wide and reflects the basically dual characteristics of ependymal cells: epithelial and glial phenotypes. The present case indicates that some anaplastic ependymomas strongly express the glial phenotype and also show remarkable anaplastic cytological features, thus closely simulating glioblastoma. The diagnostic criteria for anaplastic ependymoma, and the nosological position of highly anaplastic ependymoma and its possible clinical implications, are briefly discussed.     

MR imaging features that distinguish spinal cavernous angioma from hemorrhagic ependymoma and serial MRI changes in cavernous angioma

Cavernous angiomas of the spinal cord exhibit imaging characteristics that may overlap with those of hemorrhagic ependymoma. In the present study, we aimed to identify specific magnetic resonance imaging (MRI) findings that could be used to differentiate cavernous angioma from hemorrhagic ependymoma, and to evaluate serial MRI changes in cases of cavernous angioma. We retrospectively evaluated MR images of spinal cord tumors collected at our hospital from 2007 to 2015. From this cohort of images, 11 pathologically confirmed cavernous angiomas and 14 pathologically confirmed hemorrhagic ependymomas were compared with respect to the size of the tumor, longitudinal location, axial location, enhancement pattern, syrinx, edema, tumor margin, signal intensity of T2WI, signal intensity of T1WI, and longitudinal spreading of the hemorrhage. Serial MR images of seven spinal cavernous angiomas were reviewed. Small size, eccentric axial location, minimal enhancement, and absence of edema were more frequently observed on images of cavernous angioma compared to those of hemorrhagic ependymoma (p?<?0.01). Serial MRI changes in cases of cavernous angioma included increased longitudinal spreading of the hemorrhage (6/7, 86?%) and emergence of high signal intensity on T1WI (1/7, 14?%). Small size, eccentric axial location, minimal enhancement, and absence of edema are significant MRI findings that may be used to distinguish Type I and Type II spinal cavernous angiomas from hemorrhagic ependymomas. Furthermore, longitudinal spreading of the hemorrhage may be observed on follow-up MRIs of cavernous angiomas.     

Prognostic value of Ki-67 (MIB-1) and p53 in ependymomas

To determine whether Ki-67 (MIB-1) and p53 have prognostic value in ependymomas, clinicopathologic study was undertaken in 29 patients with this tumor. The clinical course correlated well with the histological grade according to the World Health Organization (WHO) grading system, and it was the worst in patients with anaplastic ependymoma. The percent expression of MIB-1 and p53 correlated with the histological grade of malignancy. With regard to the subtypes of benign ependymoma, the clinical course was the worst in clear-cell ependymoma, which had a significantly higher expression of MIB-1 and p53 than the other subtypes. Tanycytic ependymoma showed the most benign clinical course and the lowest expression of MIB-1 and p53. Although the WHO grading generally tended to correlate with the clinical course of ependymomas, these two subtypes-clear-cell ependymoma and tanycytic ependymoma-exhibited biological properties different from those of other grade II ependymomas.     

Influence of radiotherapy treatment concept on the outcome of patients with localized ependymomas

PURPOSE: To assess the outcome of 57 patients with localized ependymomas treated with radiotherapy (RT). METHODS AND MATERIALS: Fifty-seven patients with localized ependymomas were treated with RT. Histology was myxopapillary ependymoma (n = 4), ependymoma (n = 23), and anaplastic ependymoma (n = 30). In 16 patients, irradiation of the craniospinal axis (CSI) was performed with a median dose of 20 Gy. Forty-one patients were treated with local RT, with a local dose of 45 Gy to the posterior fossa, including a boost to the tumor bed of 9 Gy. In 19 patients, the tumor bed was irradiated with a median dose of 54 Gy. RESULTS: Overall survival after primary diagnosis was 83% and 71% at 3 and 5 years. Five-year overall survival was 80% in low-grade and 79% in high-grade tumors. Survival from RT was 79% at 3 and 64% at 5 years. We could not show a significant difference in overall survival between CSI and local RT only. Freedom of local failure was 67% at 5 years in patients treated with CSI and 60% at 5 years after local RT. A rate of 83% for distant failure-free survival could be observed in the CSI group as opposed to 93% in the group receiving local RT only. CONCLUSION: Local RT in patients with localized tumors is equieffective to CSI. The radiation oncologist must keep in mind that patients with localized ependymomas benefit from local doses > or =45 Gy.     

Role of platelet derived growth factor receptor (PDGFR) over-expression and angiogenesis in ependymoma

New molecularly targeted therapies are needed for childhood ependymoma. Angiogenesis and the PDGFR pathway could be potential therapeutic targets. This study aimed to screen ependymomas for the expression and clinicopathological correlates of angiogenic factors and potential therapeutic targets including VEGFR, endoglin (CD105), CD34, CD31, c-Kit, PDGFR-α and PDGFR-β. Immunohistochemistry for angiogenesis factors and PDGFR-α and β was performed in 24 archival tumor samples from children and adults treated for ependymoma at our institution. CD31 density, CD105 density and pericyte coverage index (PCI) were calculated. These findings were correlated with clinical outcome. VEGFR2 was overexpressed in tumor cells in only one out of 24 cases, but was found overexpressed in the vessels in 6 cases. PDGFR-α and β were found to be over-expressed in the ependymoma tumor cells in seven out of 24 cases (29.2 %). CD31 density, CD105 density and PCI did not correlate with expression of PDGFRs. Overexpression of PDGFR-α and β in tumor cells and overexpression of PDGFR-α in tumor endothelium had prognostic significance and this was maintained in multivariate analysis for overexpression of PDGFR-α in tumor cells (2 year progression free survival was 16.7 ± 15.2 for cases with overexpression of PDGFR-α in the tumor vs. 74.5 ± 15.2 for those with low/no expression, hazard ratio = 5.78, p = 0.04). A number of angiogenic factors are expressed in ependymoma tumor cells and tumor endothelium. Preliminary evidence suggests that the expression of PDGFRs could have a prognostic significance in ependymoma. This data suggests that PDGFRs should be further evaluated as targets using novel PDGFR inhibitors.     

Analysis of chromosome 7 in adult and pediatric ependymomas using chromogenic <Emphasis Type="Italic">in situ</Emphasis> hybridization

Few studies have yielded reliable data that distinguish between ependymal neoplasms based on molecular genetic attributes. The present study utilizes chromogenic in situ hybridization (CISH), a relatively recent hybridization technique, to retrospectively examine chromosome 7-copy number in pediatric and adult ependymomas. Of the 27 hybridizations, polysomy of chromosome 7 was detected in 10 out of 15 (66%) adult ependymomas, and in only three out of 12 (25%) pediatric lesions. All myxopapillary ependymomas showed polysomy. The remaining tumors were diploid. The authors conclude that (1) there are distinct genetic subsets of ependymoma, in particular, increases in copy number of chromosome 7 are almost exclusively found in myxopapillary ependymoma, and that (2) CISH is a rapid and sensitive method of stratifying morphological variants of ependymoma and potentially other central nervous system (CNS) tumors. These results encourage further investigations with CISH on a larger scale to determine its merit as an ancillary diagnostic and prognostic tool.     

Differential expression of somatostatin receptors in ependymoma: implications for diagnosis

Somatostatin receptors (SSts) have been found in a variety of brain tumors, e.g., meningiomas, medulloblastomas and astrocytomas. Our aim was to investigate their expression in ependymomas. Using RT-PCR, expression of mRNA for the different SSt subtypes was analyzed and quantified in 28 ependymomas and correlated with different variables (age, tumor location, histological grade, recurrence and survival). In addition, in 8 cases, protein expression was studied in vitro, using immunohistochemistry, and in vivo, by somatostatin scintigraphy. mRNAs for all 5 subtypes were variably expressed in each ependymoma. The Southern blotting signal obtained after SSt(1) and SSt(2) amplification was higher than that for the other receptor subtypes. No significant correlation was seen between the level of SSt(1) and SSt(2) mRNA expression and age, location, histological grading, recurrence or survival. In the 8 cases, SSt(1) staining was negative in 3 and low in 5. Staining for SSt(2A) was positive but low in every specimen analyzed. SSt(1) and SSt(2) immunoreactivity was seen only in the cytoplasm of tumoral cells. Somatostatin scintigraphy showed clear uptake, which agreed with MRI data in the majority of cases. However, no correlation was seen between tracer uptake intensity and histological grade, SSt(1) and SSt(2) mRNA expression or immunostaining intensity. This evidence for the expression of SSt(2) receptors in ependymomas opens interesting prospects for their follow-up.     

Expression of estramustine-binding protein in ependymomas and in human and developing rat ependymal cells

Summary The mainstays of primary treatment of ependymoma are aggressive surgery followed by radiotherapy. Although spreading occasionally occurs in the cerebrospinal pathways, chemotherapy is still not established and no ultimate drug has so far been found. Estramustine-phosphate (EMP), with a demonstrated effect on astrocytomain vitro, has been shown to penetrate the blood-tumor barrier and to accumulate in human brain tumor tissue including ependymoma. It has been proposed that the cytotoxic effect of EMP depends on the presence of a binding protein, estramustine-binding protein (EMBP). In the present paper we have, for the first time, immunohistochemically demonstrated an EMBP-like protein in a series of ependymomas. Immunoreactivity was found within the cytoplasm of the tumor cells with a tendency to increase with increasing malignancy of the tumor. In addition, the occurence of EMBP-like protein was demonstrated in human ependymal cells. In the rat brain, a weak immunoreactivity was detected in early fetal neuroepithelial cells while the staining intensity was increased in mature ependymal cells in late fetal, neonatal, and adult rat. Thus, immunoreactivity for an EMBP-like protein was demonstrated in ependymoma tissue, normal human ependyma and in the developing rat ependymal cells.     

Adenomatoid tumor of the ovary: an immunohistochemical and ultrastructural study

A rare case of adenomatoid tumor arising in the ovary is presented. At autopsy on a 61-year-old woman, a soft, solid and cystic tumor, measuring 0.8 X 0.7 cm, was detected in the hilus of the left ovary. Light microscopic study showed characteristic features of adenomatoid tumor. Alcian blue stain, with and without hyaluronidase pretreatment, revealed the presence of hyaluronic acid on the luminal surface and in the vacuoles of the tumor cells. Immunohistochemical stains of tumor cells were positive for low-molecular-weight cytokeratin (PKKL), vimentin, and carbohydrate antigen (CA) 125, whereas they were focally positive for high-molecular-weight cytokeratin (34 beta E12). They were negative for factor VIII-related antigen (FVIII-RAG), Ulex europaeus I lectin (UEA I), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Ultrastructural studies disclosed surface microvilli and bundles of tonofilaments. These observations strongly support the idea of this tumor being of mesothelial origin.