[Treatment concepts in osseous manifestations of Langerhans cell histiocytosis].

Introduction: Patients with Langerhans Cell Histiocytosis (LCH or Eosinophilic granuloma) were assessed from the orthopaedic point of view to give recommendations for the management of the disease.

Material And Methods: The results of 36 cases of histologically proven bony manifestations out of 48 treated cases were reviewed. A retrospective analysis of our treated cases with bony manifestations of LCH between 1970 and 1995 was performed.

[Telomere lengths and telomerase activity in liposarcomas].

We measured telomerase activity in 36 malignant and seven benign lipomatous neoplasias from 34 patients to assess the role of telomerase in the development of liposarcoma. The sensitive PCR-based telomerase assay (telomeric repeat amplification protocol-TRAP) was applied. We correlated telomerase activity with the shortening or elongation of telomeric repeat fragment length (TRF), measured by using hybridization with a telomere specific oligonucleotide probe.

[Genetic instability in osteoblastic tumors of the skeletal system].

In the histological differential diagnosis of osteoblastic bone tumors, several problems could not have been solved by conventional histological methods including immunohistology. Some well-known examples are the differential diagnosis between aneurysmal bone cyst and telangiectatic osteosarcoma and giant cell tumor versus giant cell-containing highly malignant osteosarcoma. As a new approach to these diagnostic problems, we analyzed the genetic instability in a larger number of bone-forming tumor-like lesions, benign and malignant osteoblastic tumors.

Protease expression in dedifferentiated parosteal osteosarcoma.

Background: Parosteal osteosarcoma with dedifferentiation provides a useful model to study tumor progression from an indolent locally aggressive neoplasm to highly lethal metastasizing malignancy. Up-regulation of the proteolytic enzymes participating in stromal degradation is known to promote invasive growth and metastasis of several human and experimental tumors.

Methods: The expression patterns of urokinasase plasminogen activator (u-PA), its cell-surface receptor (u-PAR), and cathepsin B were analyzed by immunohistochemical techniques in 11 cases of parosteal osteosarcoma and in 4 cases of dedifferentiated parosteal osteosarcoma.

Telomeric lengths and telomerase activity in liposarcomas.

To assess the role of telomerase in the development of liposarcomas, we measured telomerase activity in 36 malignant and seven benign lipomatous neoplasias from 34 patients. A sensitive polymerase chain reaction-based telomerase assay (the telomeric repeat amplification protocol) was applied. Shortening or elongation of telomeric repeat fragment lengths, as measured by using hybridization with a telomere-specific oligonucleotide probe, was correlated with the presence of telomerase activity.

MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas.

Purpose: The present study aimed to investigate the status of alterations of the MDM2, Rb and p53 genes in a series of 45 liposarcomas. Furthermore, the possible correlation with histological and clinical parameters was studied.

Methods: MDM2 amplification was examined by non-radioactive Southern blot hybridization with a human MDM2 cDNA probe.

p53 gene mutations in osteosarcomas of low-grade malignancy.

Alterations in tumor suppressor gene p53, localized on chromosome 17p13, are considered to play a significant role in the initiation and, to some extent, even in the progression of various malignant tumors. In this respect, investigations on conventional highly malignant osteosarcomas have shown a mutation rate of approximately 20%. However, currently, data on the mutation rate in the group of variant histology osteosarcomas of low-grade malignancy do not exist.

Genetic instability in osteoblastic tumors of the skeletal system.

At the histological level, the differential diagnosis of osteoblastic bone tumors is characterized by several problems that cannot be solved by conventional histological methods including immunohistology. Differentiating aneurysmal bone cyst from telangiectatic osteosarcoma or giant cell tumor from giant cell-containing highly malignant osteosarcoma are only two examples reflecting the complexity of this field. To develop a new approach to these diagnostic problems, we analyzed the genetic instability in a large number of bone-forming tumor-like lesions as well as in benign and malignant osteoblastic tumors.

No correlation of c-myc overexpression and p53 mutations in liposarcomas.

Although it is well known that oncogenesis is a multistep process involving the activation of normal cellular genes to become oncogenes and/or the inactivation of tumor suppressor genes, this process has seldom been investigated in soft tissue tumours. We screened a group of 36 liposarcomas for genetic abnormalities in the p53 tumour suppressor gene and c-myc oncogene. Altered c-myc gene expression was examined by differential RT-PCR assay.

Clinicopathologic implications of MDM2, p53 and K-ras gene alterations in osteosarcomas: MDM2 amplification and p53 mutations found in progressive tumors.

It is widely recognized that various oncogenes and tumor suppressor genes contribute to tumorigenesis and progression of osteosarcomas. However, whether genetic alternations enable us to predict the prognosis of patients with osteosarcomas is unclear. Southern blotting and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analyses were performed to search for MDM2, ras family and p53 gene alterations in 17 patients with high-grade osteosarcomas.

Gene alterations at the CDKN2A (p16/MTS1) locus in soft tissue tumors.

The CDKN2A gene (p16/MTS1) is a tumor suppressor that is frequently deleted, mutated, or inactivated by transcriptional silencing in certain tumor types and many tumor cell lines. We analyzed CDKN2A gene mutations and the frequency of loss of heterozygosity (LOH) at the CDKN2A locus in 135 soft tissue sarcomas. PCR-SSCP analysis of exons 1 and 2 of CDKN2A gene revealed only one missense mutation in codon 15 in a rhabdomyosarcoma.

On telomere shortening in soft-tissue tumors.

Purpose: Specific simple DNA repeats occur at the telomeric ends of mammalian chromosomes. Loss of (G + C)-rich repeats can result in genetic instability, associated with tumorigenesis. So far, data on telomere shortening have not been available for different types of soft-tissue tumors.

Alveolar soft part sarcoma of the uterine corpus. Report of two cases and review of the literature.

Alveolar soft-part sarcoma (ASPS) is a rare tumor of uncertain histogenesis, mainly localized in the extremities and less frequently found in the head, neck and trunk. The present report describes two cases of ASPS localized in the uterus. In general, this entity is very rarely encountered in the female genital tract.

p53 and ras mutations in Ewing's sarcoma.

The role of tumor suppressor genes and oncogenes in the development of Ewing's sarcoma has not yet been fully clarified. In this study, we analyzed the frequency of p53 tumor suppressor gene mutation in exons 4-8 by PCR-SSCP and direct sequencing, and the expression of p53-protein in Ewing's sarcoma (ES) by using immunohistochemistry. The overexpression of MDM2, which acts as a functional inactivator of p53, was studied by immunohistochemistry.

Improved detection of p53 mutations in soft tissue tumors using new gel composition for automated nonradioactive analysis of single-strand conformation polymorphism.

We report a new nonradioactive method to detect sequence changes, including single-base substitutions through shifts in electrophoretic mobility using an automated fluorescence sequencer (ALFexpress, Pharmacia, Biotech) connected to external cooling equipment. Single strands were identified by incorporation of fluorescein-labeled primers during amplification and subsequent laser detection at the bottom of the gel. The amplified polymerase chain reaction (PCR) products were heat-denatured and loaded onto a polyacrylamide gel under nondenaturing conditions and strict control of constant low temperature.

Expression of MDR1/p-glycoprotein and multidrug resistance-associated protein in childhood solid tumours.

We evaluated the expression of MDR1/p-glycoprotein in paediatric tumours using reverse transcriptase polymerase chain reaction (RT-PCR), RNA dot blot analysis, and immunohistochemistry on formalin fixed paraffin-embedded material with JSB-1 and C-219 monoclonal antibodies, and compared these three techniques. The expression of multidrug resistance-associated protein (MRP) gene was examined by RT-PCR assay. We studied MDR1/p-glycoprotein and MRP expression in 13 samples from 10 neuroblastoma patients, 11 samples from 10 nephroblastoma patients, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma and 10 benign tumours or tumour-like lesions.

Expression of P-glycoprotein in high grade osteosarcomas with special emphasis on chondroblastic subtype.

The development of chemoresistance is one of the major clinical problems in the therapy of malignant bone tumors in childhood. The expression of membrane-bound P-glycoprotein turned out to be an essential factor in the evidence of resistant tumor cells. To investigate the significance of multidrug resistance in the prognosis of highly malignant osteosarcomas, the immunohistologic expression of P-glycoprotein was investigated in the tumor tissue of 52 patients under special consideration of the histologic subtype.

Loss of heterozygosity on chromosome 9q21 (p16 gene) uncommon in soft-tissue sarcomas.

Chromosome region 9p21 contains a tumor suppressor locus (p16) that may be involved in the genesis of several kinds of malignant tumors. To characterize the role of this gene in the development of soft-tissue tumors (STTs), we investigated the frequency of loss of heterozygosity (LOH) at this locus. DNA was obtained from 77 tumors and the peripheral blood of 23 of the patients with the tumors.

p53 gene mutations in soft-tissue sarcomas--correlations with p53 immunohistochemistry and DNA ploidy.

The significance of p53 mutations in a group of 67 soft-tissue tumors was examined using single-strand conformation polymorphism and direct sequencing analysis. Molecular findings were correlated with immunohistochemical detection of the p53 protein and DNA ploidy status. Mutations of the p53 gene were detected in 13 (19.

Expression of plasminogen activators and plasminogen activator inhibitor 1 in dedifferentiated chondrosarcoma.

Background: The plasminogen activator system plays an important role in different malignant tumors. These enzymes participate in the destruction of intercellular matrices and basement membranes and/or can modulate the growth potency of tumor cells and may even promote metastases. In this study, the expression of three glycoproteins that play a role in the plasminogen activator system as activators of proteolysis-urokinase type plasminogen activator (u-PA), tissue type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were studied in various components of dedifferentiated chondrosarcomas of bone.

Desmoplastic small round cell tumor.

Desmoplastic small round cell tumor is an undifferentiated tumor associated with serosal surfaces, especially the peritoneum. It is found predominantly in adolescents and young adults and is much more common in males than in females. The tumor has a characteristic histology, with extensive stromal tissue around islands of small and undifferentiated cells revealing the desmoplastic appearance.

Mutation spectrum of p53 gene in highly malignant human osteosarcomas.

In this study, we analyzed the spectrum of p53 tumor suppressor gene mutations in 40 highly malignant osteosarcomas, one osteosarcoma metastasis, and one osteoblastoma with malignant transformation. Using predominantly formalin-fixed and paraffin-embedded material, we performed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of exons 4-8 and direct sequencing. Molecular genetic findings were correlated with immunohistochemical detection of p53 protein.

Aggressive osteoblastoma with focal malignant transformation and development of pulmonary metastases. A case report with a review of literature.

We report the case of a 57-year-old woman with an unusually fast-growing and destructive osteoblastic tumor affecting the left humeral head. On histopathologic examination, most of the initial tumor revealed the characteristic morphologic features of a benign-appearing aggressive osteoblastoma. Based upon the presence of a few small scattered areas composed of atypical osteoblasts in abundant lace-like osteoid showing vascular permeation, the definitive diagnosis was that of an osteoblastoma with focal malignant transformation to well-differentiated osteosarcoma.

[Pathology of Ewing sarcoma].

Ewing's sarcoma is a very rare tumor which has, however, attracted much oncological interest since the dramatic improvement of its prognosis under chemotherapy. Its histogenesis has been discussed controversially for a long time, including a possible origin in immature reticulum, myogenous, endothelial and undifferentiated mesenchymal cells. Repeated reports have also suggested a possible neuroectodermal genesis.