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Biomedical subjects

S Blasius

Publications and source records attributed to S Blasius.

At least 55 records · Page 3Linked to original sources

Diagnostic value of the molecular genetic detection of the t(11;22) translocation in Ewing's tumours.

One consistent feature of the Ewing's tumour family is the presence of a balanced translocation involving band q12 and band q24 of chromosome 22 and chromosome 11. Recent cloning of the chromosome breakpoint regions of t(11;22)(q24;q12) Ewing's sarcoma translocation has revealed that the breakpoints were localized within the Ewing's sarcoma gene (EWS gene) on chromosome 22 and the Fli-1 gene on chromosome 11. Molecular genetic techniques can thus be applied to the detection of the t(11;22) translocation in Ewing's tumours. By reverse transcription and polymerase chain reaction technique (RT-PCR) 11 Ewing's tumour derived cell lines, 12 primary Ewing's tumours, and 11 tumours after treatment were analysed for the occurence of the t(11;22) translocation. Furthermore, blood and bone marrow samples from 5 patients were available for RT-PCR. In 78% of the cell lines and 91% of the primary Ewing's tumours the t(11;22) translocation was detectable by RT-PCR. In bone marrow samples from a Ewing's sarcoma patient presenting in relapse tumour cells were detected by molecular genetic analysis. Our results indicate that molecular genetic detection of the t(11;22) translocation is valuable in the differential diagnosis of small round cell tumours and will provide important information for the staging and prognosis of Ewing's tumour.

Base Sequence↗

[Molecular genetic detection of t(11;22)(q24;12) translocation in Ewing sarcoma and malignant peripheral neuroectodermal tumors].

Ewing's sarcomas and malignant peripheral neuroectodermal tumors (MPNTs) show very little evidence of differentiation and lack characteristic morphological features at the light-microscopic level. These malignancies have always presented a significant differential diagnostic challenge to the pathologist. Electron microscopy, immunohistochemical staining for neural antigens such as neuron-specific enolase (NSE), Leu 7, synaptophysin and, more recently, the detection of Mic-2 gene expression have been included in the routine histopathological diagnostic procedure. However, the expression of these antigens is not restricted to this entity. Thus, further modalities are required to prove diagnostic reliability. One consistent feature of the Ewing's sarcoma family is the presence of the reciprocal chromosomal t(11;22)(q24;q12) translocation. Recent cloning of the t(11;22) break point has led to the identification of the genes involved in this translocation. This provides the possibility of molecular genetic detection of the t(11;22) translocation in Ewing's sarcomas and MPNTs. We have established a method using reverse transcription and the polymerase chain reaction (RT-PCR) for the detection of the specific gene fusion transcript caused by the 11;22 translocation. The validity of our approach was proved by analyzing Ewing's tumor cell lines and tissue material obtained from primary biopsies and tumor resections. Molecular genetic detection of the 11;22 translocation by RT-PCR analysis should perhaps be included in the diagnostic work-up of suspected Ewing's sarcoma and MPNT.

Bone Neoplasms↗

Intravascular lymphomatosis of the CNS: clinicopathologic study and search for expression of oncoproteins and Epstein-Barr virus.

Five cases of intravascular lymphomatosis (IVL) are reported. Diffuse or focal cerebral signs suggestive of vascular disease occurred in four cases, but case 5 presented with symptoms similar to Creutzfeld-Jakob disease. Clinical course ranged from two to eight months and diagnosis was made in all cases by autopsy. Neoplastic lymphoid cells mainly lodged in lumina of small vessels in many organs, but infarction was confined to the CNS. Some extravascular tumor cells were regularly seen. All cases corresponded to high-grade Non-Hodgkin lymphomas of B-cell type and displayed high proliferation indices. Different from findings in primary cerebral and nodal lymphomas, neither p53 nor bcl-2 oncoproteins were detectable. Absence of EBV genome and EBV latent membrane protein from IVL was demonstrated for the first time.

Aged↗

Anaplastic thyroid carcinoma with osteosarcomatous differentiation.

A case of a thyroid tumour with the cytological and histological pattern of anaplastic carcinoma with extensive osteosarcomatous differentiation in a 54-year-old Kaukasian woman is presented. Immunohistochemical examination revealed keratin-vimentin co-expression in anaplastic tumour areas. According to the WHO classification of thyroid tumours the present tumour has to be classified as an anaplastic carcinoma. A retrospective survey revealed only twenty-four comparable cases in the literature. The present tumour most likely represents an example of a neoplastic epithelial-mesenchymal metaplasia. The possible mechanisms of the occurrence of thyroid tumours with mixed epithelial-mesenchymal differentiation are briefly discussed.

Carcinoma↗

[Significance of intravascular ultrasound in arteriosclerotic calcified intima plaques: in vitro comparison of 20 and 12.5 MHz transducers].

The aim of this in vitro study was to analyze the diagnostic performance of intravascular ultrasound (IVUS) in vessel wall calcifications and to compare the accuracy of mechanical 12.5 and 20 MHz transducers. Fourty-three sections of 10 vessels with signs of arteriosclerotic disease on pathologic examination were examined. Slices 500 microns thick were obtained and examined radiographically at 9 fold magnification. In each section, identical segments were defined, amounting to a total of 344 segments. The IVUS sections were analyzed by 3 experienced readers. For statistical evaluation ROC analysis was performed using magnification radiography as a reference. An area under the curve (AUC) of 0.79 was obtained for the 12.5 transducer and of 0.83 for the 20 MHz transducer. Additionally, sensitivity, specificity, and accuracy were determined. Sensitivity depended on the morphology, size, and density of the calcified lesions. We therefore conclude that the sensitivity of intravascular ultrasound concerning calcified arteriosclerotic plaques is limited and that there is no significant (p < 0.01) difference between mechanical 20 and 12.5 MHz transducers in examining iliac arteries.

Angiography↗

In vitro correlation of intravascular ultrasound and direct magnification radiography for calcified arterial lesions.

RATIONALE AND OBJECTIVES: Intravascular ultrasound (IVUS) is an adjunct to contrast angiography that gives additional information concerning the morphology of the vascular wall. The authors examined the accuracy of intravascular ultrasound (IVUS) in the evaluation of calcified lesions within the abdominal aorta and the iliac artery. METHODS: Forty-nine human specimens (iliac artery, 26; abdominal aorta, 23) were examined using a 20-MHz 6.0-F ultrasound catheter, followed by magnification radiography of the same specimens using a newly developed microfocus x-ray tube. Magnification radiographs and ultrasound images were divided into identical sectors to analyze the morphology of calcified arteriosclerotic lesions. RESULTS: A total of 644 sectors was analyzed. Sensitivity of intravascular sonography was 70%, specificity 53%. Sensitivity strongly depended on the morphology of the calcified lesions. CONCLUSION: The detection of calcified arteriosclerotic lesions by means of IVUS revealed a sensitivity of 70% in an in vitro study using human specimens. However, the specificity of IVUS was only 53%, which is basically a random chance occurrence.

Aorta, Abdominal↗

[Detection of EWS-/FLI-1 gene fusion transcripts by RT-PCR as a tool in the diagnosis of tumors of the Ewing sarcoma group].

Recent cloning of the chromosome breakpoint regions of the reciprocal chromosomal t(11;22) (q24;q12) has revealed that the breakpoints were localized within the EWS gene (Ewings sarcoma gene) on chromosome 22 and the FLI-1 gene on chromosome 11. Thus, molecular genetic techniques were applicable for the detection of this genetic aberration, which occurs as a consistent feature of the Ewings tumor family. By reverse transcription and polymerase chain reaction technique (RT-PCR) in 78% of Ewings sarcoma derived cell lines, and in 91% of primary Ewings tumor tissue t(11;22) specific EWS/FLI-1 fusion transcripts were detected. Furthermore, in bone marrow samples from an Ewings sarcoma patient contaminating tumor cells could be shown by RT-PCR. Our results indicate that molecular genetic detection of the t(11;22) translocation opens a new modality for the differential diagnosis and the staging of Ewings tumor patients.

Base Sequence↗

[Transthoracic punch biopsy of mediastinal tumors].

48 consecutive patients underwent biopsy of anterior mediastinal tumors under sonographic guidance by the use of cutting needles up to 2.0 mm in diameter. The results of needle biopsies were compared with the final diagnoses, which was proved with pathologic studies or clinicoradiologic follow-up. In 39 (93%) of 42 malignant tumors malignancy could be readily diagnosed. Examinations of the microcylinders of tissue resulted in correct histologic diagnoses in 32 (76%) of 42 malignant tumors including 13 (81%) of 16 Hodgkin's lymphomas, 6 (66%) of 9 non-Hodgkin lymphomas, 2 (66%) of 3 thymomas and 9 (82%) of 11 carcinomas. All 6 benign lesions were correctly identified. No complications such as hemorrhage or pneumothorax were encountered.

Adolescent↗

Immunohistochemical localization of PDGF B, PDGF beta receptors and IGF I receptors during atherogenesis.

Growth factors and their receptors may be involved in initiation and progression of atherosclerotic intima changes. In this study, sections of human arteries in different stages of atherosclerosis were investigated for cellular expression of PDGF B, PDGF beta receptors and IGF I receptors. The applied immunohistochemical approach detected IGF I receptor synthesis in endothelial cells of atherosclerotic vessels. A possible role in atherogenesis may be seen in the control of IGF I transfer into subendothelial tissues. PDGF B chain production was observed in endothelial cells and macrophages in all stages of lesion development. The corresponding receptor for PDGF B (PDGF beta receptor) was expressed by transformed smooth muscle cells within the thickened intima from the stage of macrophage infiltration onwards. These results support the thesis that locally produced PDGF acts as a mitogen on smooth muscle cells and may promote proliferation during atherogenesis.

Animals↗

Plasminogen activators and their inhibitor in osteosarcomas and other bone tumors.

The concentrations of the plasminogen activators u-PA and t-PA as well as the inhibitor PAI-1 were studied immunohistochemically in 35 osteosarcoma specimens compared to 15 Ewing's sarcomas and various other bone lesions. The immunoreactivities of plasminogen activators in osteosarcoma specimens were significantly higher than PAI-1. Biochemically in cell cultures and immunohistochemically in the pathological specimens of the osteosarcomas u-PA was the dominant antigen, all factors showing a generally strong reactivity. Here a relation to the malignancy and invasivity of the tumors could be seen, which was comparable to the results in other tumors. This correlation, however, could not be detected in Ewing's sarcomas. On the whole low immunoreactivity of all enzymes, and of u-PA in particular, could be seen. In comparison in some benign lesions (fibrous dysplasias, aneurysmal bone cysts) the immunohistochemical reactions were distinctly stronger. Dominant antigens did not exist in Ewing's sarcomas. In all mesenchymal tumors studied the immunohistochemical localisation and concentration of the antigens showed a definite correlation with their histological differentiation. Chondroblastic differentiations in different tumors (chondrosarcomas, enchondromas, chondroblastic osteosarcomas) or chondroid parts were always negative for both activators and the inhibitor, especially in their central parts. Here, the biological malignancy was not decisive for the result.

Bone Neoplasms↗

Chondromyxoid fibroma of the sternum. Case report.

We report the second case of chondromyxoid fibroma (CMF) of the sternum, documented in the literature. In this case, only histology of the biopsy was useful in diagnosing CMF before definitive surgery. A wide subtotal resection of the sternum and reconstruction with a Gore-Tex soft tissue patch was performed.

Adult↗

High malignant surface osteosarcoma arising at the site of a previously treated aneurysmal bone cyst.

A patient who developed a high malignant surface osteosarcoma at the site of a previously treated aneurysmal bone cyst is reported. The patient developed the osteosarcoma 4 years after complete curettage and bone-grafting of the cyst. The clinical, radiological and light microscopic features of this case are described. A causal relationship between the preexisting aneurysmal bone cyst and osteosarcoma is discussed, but seems to be unlikely.

Adult↗

Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone.

Alterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewing's sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giant-cell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.

Adolescent↗

Prognostic implication of immunodetection of P glycoprotein in Ewing's sarcoma.

Increased expression of P glycoprotein is associated with multidrug resistance in many cell lines. P glycoprotein has been detected in different human tumors. To assess the implication of multidrug resistance in the prognosis of Ewing's sarcoma the expression of P glycoprotein was studied immunohistochemically in pre- and post-therapeutic tumor tissues of 21 cases treated according to the CESS 81 or 86 protocol. The response to chemotherapy was evaluated histologically. Formalin-fixed, paraffin-embedded and fresh frozen sections were immunostained with a monoclonal antibody to P glycoprotein, clone JSB 1, using the double APAAP method. P glycoprotein was detected in 12 cases of 21 (57%) in either pre- or postchemotherapy tumor tissues. From the 21 cases 8 revealed a good morphological response to chemotherapy (33%); 10 of the 13 non-responders were positive for P glycoprotein (77%), but only 2 of the 8 responders (25%). The difference was statistically significant (P < 0.05). Comparing P glycoprotein expression with the clinical outcome, we found that 7 of 12 positive cases had died (58%). From the negative cases only 3 of 9 had died (33%). However, judged by the Kaplan Meyer life tables, these data were not significant. In conclusion our results suggest that the immunodetection of P glycoprotein indicates a poor response to chemotherapy and probably a bad clinical outcome for Ewing's sarcoma patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Localization dependent patterns of findings in chondroblastoma].

In a retrospective study the radiographs of 48 chondroblastomas from the files of the Bone Tumour Registry of Westphalia were evaluated. The purpose of the study was to investigate whether chondroblastomas display localisation-dependent radiographic patterns. All radiographs were analysed using the Lodwick criteria. All chondroblastomas (mean age: 18 y., m:f = 1.25:1) showed a geographic pattern of bone destruction. 32 lesions affected long bones, 10 short bones, and 6 flat bones. Chondroblastomas localised in flat bones (Lodwick IA: 0%, IB: 33%, IC: 67%) demonstrated more aggressive patterns of bone destruction compared to lesions affecting long bones (Lodwick IA: 56%, IB: 31%, IC: 13%) or short bones (Lodwick IA: 40%, IB: 50%, IC: 10%). There was no difference between the three bone types in other radiographic patterns (periostitis, calcification, trabeculation).

Adolescent↗

Osteofibrous dysplasia of long bones--a reactive process to adamantinomatous tissue.

The most controversial aspect of osteofibrous dysplasia (OFD) is its possible histogenetic relationship to adamantinoma of long bone. Evidence is recently beginning to accumulate that OFD may be a reactive process to regressive adamantinoma. To verify the concept, 13 lesions of OFD were studied again by immunohistochemistry for cytokeratins of different molecular masses, as well as by conventional stainings. In addition, 2 adamantinomas and 6 fibrous dysplasias of the tibia were studied for reference. A small number of spindle- or ovoid-shaped cells scattered individually in the fibro-osseous stroma showed positive reactions for cytokeratins of 55-57 kDa in 2 lesions, and for those of 45-56.5 kDa in 8 lesions of 13 OFDs, although no definite epithelial island could be detected even by immunohistochemistry. Adamantinomas also showed single cytokeratin-positive cells dispersed in fibroblastic stroma, in addition to epithelial islands positive for cytokeratins of both 55-57 kDa and 45-56.5 kDa. All cases of fibrous dysplasia were negative for cytokeratins. During the observation, no case of OFDs progressed to classic adamantinoma. The present study, demonstrating the existence of an intermediate stage between "differentiated adamantinoma" and total elimination of adamantinomatous components, gives further support for the concept that OFD is a secondary reactive process to adamantinomatous tissue. In practice, the existence of single scattered cytokeratin-immunoreactive cells in otherwise typical OFDs may not indicate the truly malignant behaviour of classic adamantinoma, unless discrete epithelioid cell nests are also found.

Adolescent↗

(Sub)periosteal Ewing's sarcoma of bone.

Ewing's sarcoma is a small malignant round-cell tumour that arises from mesenchymal cells, predominantly in the medullary cavity of bone. In exceptional cases it originates in the soft tissues and subsequently invades the underlying bone. A (sub) periosteal origin of Ewing's sarcoma is a very rare condition: only a few cases have been published so far. Three cases of (sub)periosteal Ewing's sarcoma, having received neoadjuvant chemotherapy and radiation therapy as well as wide excision, are reported.

Adolescent↗