Biomedical subjects

A Roessner

Publications and source records attributed to A Roessner.

At least 127 records · Page 7Linked to original sources

PubMed1997

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. Using one microsatellite marker distal to p16(D9S171) and one intragenic sequence-tagged site (STS) marker (c5.1), we observed LOH in only one liposarcoma and one malignant schwannoma (2.6%). Homozygous deletions of the p16 markers were not found. The osteosarcoma cell line MG-63 was used as a control for loss of the p16 gene. Because of the low LOH frequency, we hypothesize that the p16 gene is not essential for STT oncogenesis.

Chromosomes, Human, Pair 9↗

PubMed1997

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. Peak shifts in the fluorogram indicated mutations. A novel gel composition improved the detection rate for mutations considerably. Automatic analysis of single-strand conformation polymorphism (SSCP) gels saves time and costs, and is highly reproducible. The method was applied for mutation screening in exon 7 of the p53 tumor suppressor gene in DNA of freshly frozen soft tissue tumors. The mutation spectrum and frequency in exon 7 of the p53 gene are discussed with respect to oncogenesis in soft tissue sarcomas.

Autoanalysis↗

PubMed1997

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. Eleven of 13 neuroblastomas, 7 of 11 nephroblastomas, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma, and 7 of 10 benign tumours or tumour-like lesions showed MDR1 PCR products. By RNA dot blot analysis, MDR1 transcripts were detectable in 11 of 34 specimens. Immunohistochemically, we detected positive reaction products for JSB-1 in 26 of 36 samples. There was a significant correlation between the immunoreactivity for JSB-1 and the expression of MDR1 mRNA expression by RT-PCR (P = 0.0001). However, the presence of p-glycoprotein immunostaining does not correlate with the MDR1 expression shown by RT-PCR in every case. As for MRP mRNA expression, 9 of 13 neuroblastomas and 10 of 11 nephroblastomas revealed PCR products.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma. A comparative analysis with clinico-pathological factors.

The aim of the study was to analyze p53 gene mutations and the expression of p53 and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results were then correlated with tumor grade, stage, estrogen receptor status, nodal status, and DNA ploidy. The expression of the proteins p53 and mdm2 was determined immunohistochemically using formalin-fixed, paraffin-embedded material. Screening for p53 mutation involved analysis of the highly conserved regions of the p53 gene (exons 5-9) by the polymerase chain reaction/ single-strand conformation polymorphism (PCR-SSCP) technique. PCR products with band shifts were directly sequenced. Immunohistochemical staining of p53 was positive in 9 cases (29.0%), only 2 of which showed a p53 gene mutation. These were identified as a C-->G transversion at the second position of codon 278 in exon 8 and an A-->G transition at the second position of codon 205 in exon 6. A third case with a mutation was observed (C-->T transition, position 1 of codon 250 in exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive tumors, 2 were moderately differentiated (grade II). The remaining tumors were poorly differentiated (7/9). By contrast, p53-negative carcinomas were well differentiated (grade I) in most cases (P = 0.02). DNA cytometry in 8 of the 9 p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53-negative tumors were diploid (P = 0.01). Mdm2 oncoprotein was detected in 10 tumors (32.2%), 4 of which were p53-positive, including the 3 with mutations. The grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were always noted to be mdm2-negative (P = 0.04). Overexpression of p53 protein is a complex mechanism and does not merely indicate the detection of mutations in the p53 gene. This study has shown that p53 expression correlates with tumor grade and DNA ploidy. Mdm2 expression was also associated with the tumor grade. Immunohistological demonstration of the p53 protein alone is insufficient as a basis for comment on the functional state of the p53 gene and gene product. The interrelation between recognition of the p53 protein and gene mutation needs more careful assessment to define their roles in the control of neoplasia.

Adult↗

PubMed1997

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 (19.5%) out of 67 cases of soft-tissue tumors. Only three were localized outside the conservative regions of the p53 gene. Six mutations were described for the first time in these tumors. Most of the mutations were point mutations in exons 5-8 and, in one case, a deletion at the 3'-splice site of exon 5 could be demonstrated. There was no significant correlation between the occurrence of p53 mutations and the histological grade, although a high number of mutations were defined in poorly differentiated tumors (grade 3). Molecular finding of a p53 gene mutation and immunohistochemical detection of p53 expression did not correlate, which may be due to the high percentage of nonsense mutations in our study (50%). We confirm that only DNA sequencing allows a unique identification and differentiation of mutations in the p53 gene. Other factors may be responsible for the detection of p53 protein in many cases. Histological grade correlated with aneuploidy. The frequency of mutations observed was in accordance with values quoted in the literature. Generally, p53 mutations and p53 overexpression are more likely to represent a late event in the oncogenesis of soft-tissue tumors.

Adult↗

PubMed1997

Expression of multidrug resistance-associated protein gene in Ewing's sarcoma and malignant peripheral neuroectodermal tumor of bone.

The expression of multidrug resistance-associated protein (MRP) mRNA was examined in ten samples of Ewing's sarcoma of bone (ES) and in one nude mice transplantable ES and two malignant peripheral neuroectodermal tumor (MPNT) cell lines using an RT-PCR assay. MRP mRNA expression was recognized in eight of the ten clinical specimen and in all three cell lines. On the other hand, the expression of multidrug resistance gene (MDR1) was demonstrated in three of the ten clinical samples and all three cell lines. Our results may contribute to elucidation of the mechanism of anti-cancer-drug resistance in this tumor.

ATP-Binding Cassette Transporters↗

PubMed1997

Immunolocalization of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas.

We have immunohistochemically examined the localization of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in human chondrosarcomas (CHS) (23 cases) and benign chondroid lesions (BCL) (16 cases of osteochondromas and 11 cases of enchondromas). In CHS, all the MMPs and TIMPs examined were positive. Among them, MMP-1 was immunolocalized in more than 90% of both CHS and BCL, but positive score of MMP-1 was significantly higher in CHS than that in BCL (p < 0.01). Compared with BCL, CHS expressed MMP-3 at a low level, and more often positive in MMP-9. It is possible that chondrosarcoma might have a tendency to lose the ability to secrete MMP-3, which is a metalloproteinase that can degrade cartilage proteoglycans and is related to normal cartilage turnover. MMP-2, TIMP-1 and TIMP-2 were immunolocalized in more than 70% of the cases of both BCL and CHS, but the positive scores of these were not statistically different between the two groups. Interestingly, in several cases of CHS, both MMP-1 and MMP-9 immunostains were observed preferentially within the cells at the marginal areas of cartilaginous lobules. These findings suggest that increased expression of MMP-1 and MMP-9 and decrease in MMP-3 expression are associated with the malignant phenotype of the cartilaginour tumors.

Adult↗

PubMed1997

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. The data were compared with the histologic regression grade in the resection specimen and correlated with clinical data. Formalin-fixed, paraffin-embedded tissue and, additionally, fresh frozen material taken from the primary biopsy were stained using monoclonal antibody JSB1. 29 (55%) of the tumors investigated were P-glycoprotein positive. Considering the response to chemotherapy, no conclusion could be drawn regarding P-glycoprotein expression, regression grade in the resection specimens, and the clinical follow-up. P-glycoprotein was detected in only 52% of the non-responders. A positive reaction was also evidenced in 59% of the patients with high chemosensitivity. A comparison of the histologic subtypes yielded a significant result in the chondroblastic osteosarcomas. 11 of 12 cases showed a strong expression of P-glycoprotein. Most of the cases were non-responders, and using Kaplan-Meier live tables, an unfavorable clinical outcome could be demonstrated. Possibly, chondroblastic tumors have a special position among osteosarcomas because of their differentiation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Assessment of proliferative activity, DNA values and some clinicopathologic parameters in mesenchymal tumors. Immunohistochemical and flow cytometric study.

Clinicopathologic parameters of 70 consecutive mesenchymal tumors from 63 patients were evaluated. In all these cases, the DNA content was analyzed by flow cytometry, and the expression of proliferative antigen MIB1 and p53 protein was assessed by immunohistochemistry. Our study verified the prognostic usefulness of proliferative indicators, above all MIB1-index, which strongly correlated with tumor grade and independently influenced overall survival.

Adolescent↗

PubMed1997

Hypothalamic osteolipoma: a case report.

The authors present a case of an ossified lipoma at tuber cinerum, an incidental finding when performing an autopsy of a 61-year old male. A tight connection to right communicans posterior artery led first to the diagnosis of a calcified saccular aneurysm, but histologic examination revealed an osteolipoma consisting of mature adipose tissue and formation of bone. Intracranial lipomas are neither hamartomas nor true neoplasms, but they are more likely to be congenital malformations. The recent literature is reviewed, and the two most current embryologic concepts of the development of intracranial lipomas are discussed.

Autopsy↗

PubMed1997

Small cell carcinoma of the ovary, hypercalcemic type. A case report with immunohistochemical, ultrastructural and cytophotometric analysis and review of the literature.

Small cell carcinomas of the ovary, hypercalcemic type, are unilateral tumors occurring almost exclusively in young women. 60% of the cases are associated with hypercalcemia. Microscopic examination shows diffuse clusters of small cells and follicle-like spaces. Immunohistochemically, the tumor cells are positive for epithelial and mesenchymal markers, and ultrastructurally they contain an abundance of dilated rough endoplasmatic reticulum and numerous free ribosomes. By DNA-single cell photometry, the neoplastic cells show a diploid DNA-content.

Adult↗

PubMed1997

Alterations of p53 gene in soft tissue and bone tumors.

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Adolescent↗

PubMed1997

Prevalence and pattern of Helicobacter pylori gastritis in the gastric cardia.

OBJECTIVES: Helicobacter pylori has a predilection for antral colonization. Local acid production is the major determinant of colonization. Because production is low in the antrum and cardia, H. pylori should also colonize the cardia. We therefore investigated the histologic pattern of gastritis and the prevalence of H. pylori in the cardia compared with the antrum and corpus. METHODS: From 135 H. pylori-infected patients with gastritis, ulcer disease, or reflux esophagitis, biopsies were obtained from the antrum, corpus, and cardia. The prevalence, topography, and histologic parameters of gastritis were examined. RESULTS: All 135 patients had active antral H. pylori gastritis: in the cardia, 132 of these patients (97.7%) showed active gastritis, and 124 patients (91.9%) had H. pylori visible on staining. Gastritis of the cardia in most patients resembled antral gastritis, but the density of bacteria and the inflammatory responses were less marked. The most striking finding in the cardia of patients with gastroesophageal reflux was a lower density of bacteria compared with antrum and corpus. Intestinal metaplasia was found in 32 patients in antral mucosa (23.7%) versus 28 patients in the cardia (20.7%), versus 11 patients in the corpus (8.1%), and was multifocal in 17 patients (12.6%). CONCLUSIONS: H. pylori gastritis commonly involves the cardia. The histologic density of the bacteria and inflammatory responses are lower than in the antrum. Intestinal metaplasia in the cardia is a common finding in H. pylori gastritis. The cause of the lower bacterial density in the cardia of patients with reflux esophagitis needs further investigation.

Atrophy↗

PubMed1997

Bellini duct carcinoma of the kidney--a case report.

Bellini duct carcinoma (BDC), originating from the principal cells of the collecting duct of the kidney, accounts for only 1% of renal carcinomas. This lesion is a histogenetically, morphologically and cytogenetically defined entity. We report an eosinophilic variant of BDC. A 71-year old male presented with a tumor in the right kidney. Nephrectomy was performed. BDC (stage pT3a N0 M0 G2, based on UICC classification) was diagnosed. Electron microscopy revealed an abundance of mitochondria. Intranuclear rodlets were seen. Neuroendocrine differentiation was not demonstrated. After a three-year observation period, there are no signs of recurrence or metastases.

Aged↗

PubMed1996

Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas.

We examined the mRNA expression of the multidrug- resistance-associated protein gene (MRP) in soft-tissue sarcomas and compared it with the expression of the multidrug resistance gene (MDR1), using the reverse transcriptase/polymerase chain reaction. We investigate 39 samples from 33 cases of soft-tissue sarcomas (11 liposarcomas, 9 malignant fibrous histiocytomas, 6 leiomyosarcomas, 4 malignant schwannomas, 3 fibrosarcomas, 3 synovial sarcomas, and 3 epithelioid sarcomas) and 7 benign soft-tissue tumors. All samples were obtained prior to chemotherapy. An expression of MRP mRNA was noted in 56% of soft-tissue sarcoma specimens. The co-expression of MRP and MDR1 was recognized in 15 samples (38%) (5/11 liposarcomas, 5/9 malignant fibrous histiocytomas, 3/6 leiomyosarcomas, 2/3 fibrosarcomas) and significantly correlated with histological grade (P=0.0165). A positive and significant correlation was found between MRP and MDR1 expression in soft-tissue sarcomas(P=0.0013). In benign soft-tissue tumors, 1 chemodectoma and 1 neurothekeoma showed low MRP expression; however, no case showed co-expression of MRP and MDR1.

ATP-Binding Cassette Transporters↗

PubMed1996

[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. Convincing arguments, however, have only been brought forward during recent years, since it was found that Ewing's sarcoma and malignant peripheral neuroectodermal tumor share a common chromosome translocation 11;22. In the meantime this hypothesis has been strengthened by numerous cell biological analyses. There seems to be no clear border between Ewing's sarcoma and malignant peripheral neuroectodermal tumors with definite neural differentiation. Histological differential diagnosis of Ewing's sarcoma has been improved by immunohistological methods. In most cases, they can be distinguished from lymphoma (leucocyte common antigen, B and T markers) and embryonal rhabdomyosarcoma (muscle specific actin, desmin) without problems. Apart from that, it is possible nowadays to obtain antibodies against the MIC 2-protein, which is preferably expressed in Ewing sarcoma. The diagnostics of Ewing's sarcoma and the malignant peripheral neuroectodermal tumor have considerably been enriched by the fact that the specific chromosome translocation t(11;22) can be proved molecular biologically. In contrast to the cytogenetic evidence, it is not necessary to establish cell cultures.

Biomarkers, Tumor↗

PubMed1996

Reverse transcriptase-polymerase chain reaction amplification of MDR1 gene expression in adult soft tissue sarcomas.

Expression of the multidrug resistance gene MDR1 is reported to be an important determinant of the response to chemotherapy and survival in some cancers. We compared three methods for determining the intrinsic MDR1 expression in soft tissue sarcomas. We studied MDR1 gene expression in 39 samples from 33 cases of soft tissue sarcomas comprising 11 liposarcomas, nine malignant fibrous histiocytomas, six leiomyosarcomas, four malignant schwannomas, three fibrosarcomas, three synovial sarcomas, and three epithelioid sarcomas, and seven cases of benign soft tissue tumors in adult patients. To detect MDR1 mRNA, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in all samples. Furthermore, RNA dot-blot analysis with digoxigenin-labeled RNA probe and immunohistochemistry with JSB-1 and C-219 antibodies for P-glycoprotein were employed in 34 and 37 samples in soft tissue sarcomas, respectively. We compared these three detection techniques. Of the 39 specimens, 18 (46%) showed MDR1 PCR products. Liposarcomas (six of 11), malignant fibrous histiocytomas (six of nine), leiomyosarcomas (four of six), fibrosarcomas (two of three) revealed high or intermediate MDR1 expression at high frequency. No MDR1 expression was detectable in malignant schwannomas, synovial sarcomas, or epithelioid sarcomas. Of seven benign soft tissue tumors, one ganglioneuroma and one lipomatosis showed low levels of MDR1 expression. By RNA dot-blot analysis, MDR1 transcripts were detectable in 12 of 34 specimens (35%). Four samples were negative by dot blot despite positivity with RT-PCR. Concordance between MDR1 expression by RNA level with RT-PCR and dot blot and at the protein level with immunohistochemistry using C-219 was found in 16 (47%) of the 34 comparable specimens. Eight samples showed positive immunoreactivity for C-219 despite negative results in RT-PCR and dot-blot analysis. The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma. For the evaluation of MDR1 expression, RT-PCR is useful because of its relative simplicity and sensitivity. However, the clinical significance of such low levels of MDR1 expression detected only by RT-PCR must be discussed within systematically treated patient groups.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Expression of the adhesion molecules ICAM, VCAM, and ELAM in the arteriosclerotic plaque.

Subject of investigation was the demonstration of the different expression of ICAM-1, and VCAM in 13 complete cross sections of the Aorta abdominalis and the Arteria iliaca immediately available post operationem during the process of arteriosclerosis. With increasing severity of the arteriosclerosis, ELAM showed a decreasing expression of the endothelium of the main vessel and a moderate one of the cells in the adventitia. On the endothelium of the main vessel and the vasa vasorum, we detected ELAM-1, showing a decreasing tendency when the arteriosclerosis was aggravating. In case of severe arteriosclerosis, a focal expression was also found on cells in the intima and media. In the adventitia, the expression was relatively constant during the process of arteriosclerosis. The more serious the disease, the more provable was VCAM on endothelial cells. In cases of severe arteriosclerosis, we also detected a focal staining in deeper layers of the wall. This study supports the concept of the active role of endothelial cells in the recruitment of leucocytes during the early steps of the arteriosclerotic process. In this process, with the disease aggravating, the endothelium seems to be less significant than the smooth muscle cells, which obviously play an important role in the course of arteriosclerosis.

Aorta, Abdominal↗