bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of integrins and CD44 isoforms in non‐Hodgkin's lymphomas: CD44 variant isoforms are preferentially expressed in high‐grade malignant lymphomas
Authors: Terpe Hans‐Joachim , Koopmann Rita , Imhof Beat A. , Günthert Ursula 
Published: June 2005

AbstractLow‐ and high‐grade malignant non‐Hodgkin's lymphomas have been investigated by immunohistochemistry for their expression of various integrins and CD44 isoforms. Comparison with the expression patterns obtained in non‐malignant adult lymph nodes revealed the following differences: α6 and β4 integrins were expressed in several high‐grade malignant lymphomas to a lower degree than in both the low‐grade malignant lymphomas and the normal lymph nodes; all other integrins (α2, α4, α5, αv, β1, β2, β3, and β7) did not exhibit significant differences in the expression levels between malignant and non‐malignant tissues. The standard isoform of CD44 (CD44s) was highly expressed in all lymphoid tissues. Using CD44 exon‐specific monoclonal antibodies, CD44 variant isoforms were not detected in non‐malignant lymph nodes and were detected only rarely in low‐grade malignant lymphomas. In contrast, high‐grade malignant lymphomas expressed several CD44 variant isoforms, which included the products from the variant exons 3v, 6v, and 9v, but not 4v. Specifically, detection of exon 3v and 6v products indicates a more aggressive phenotype.
Expression of E‐cadherin (E‐CD) as related to other prognostic factors and survival in breast cancer
Authors: Lipponen P. , Saarelainen E. , Ji H. , Aaltomaa S. , Syrjänen K. 
Published: June 2005

AbstractA series of 208 breast cancer biopsies were analysed immunohistochemically for expression of E‐cadherin (E‐CD). Altogether, 72 per cent of the tumours showed E‐CD positivity in over 50 per cent of cells, the staining being heterogeneous in nearly all tumours. In only 16 per cent of ductal carcinomas was positive staining seen in less than 1 per cent of cells. Expression of E‐CD was not related to tumour diameter, nodal status, metastasis at diagnosis, histological grade, DNA ploidy, S‐phase fraction, nuclear area, mitotic frequency, or PR content. There was a significant relationship between expression of E‐CD, histological type (P=0.01), the proportion of intraductal growth (P=0.008), the density of tumour‐infiltrating lymphocytes (P=0.0007), ER content (P=0.012), and morphometric nuclear factors (P=0.02). Expression of E‐CD showed a weak association with a high survival probability (P=0.02), while the relation to recurrence‐free survival was not significant (P=0.11). In axillary lymph node‐negative tumours, E‐CD expression was not related significantly to survival (P=0.11) or to recurrence‐free survival (P=0.06). In multivariate analysis, E‐CD expression had no independent prognostic value, while the axillary lymph node status, tumour diameter, patient age, and mitotic frequency were independent prognostic factors. The results indicate that E‐CD expression is related to several histological features in breast cancer, but has no independent prognostic value over standard prognostic factors.
Demonstration of skin‐derived antileukoproteinase (skalp) and its target enzyme human leukocyte elastase in squamous cell carcinoma
Authors: Alkemade Hans A. C. , van Vlijmen‐Willems Ivonne M. J. J. , van Haelst Urbaan J. G. M. , van de Kerkhof Peter C. M. , Schalkwijk Joost 
Published: June 2005

AbstractSkin‐derived antileukoproteinase (SKALP), also known as elafin, is a strong and specific inhibitor of elastase and proteinase 3. SKALP is not present in normal epidermis, but is expressed by epidermal keratinocytes under hyperproliferative conditions such as psoriasis, wound healing, and in cell culture. In human epidermal tumours, SKALP is differentially expressed and restricted to tumours with distinct squamous differentiation. We have studied the presence of both SKALP and one of its known target enzymes, leukocyte elastase, in 41 squamous cell carcinomas of the skin. SKALP expression correlated with the degree of differentiation: strong expression was seen in well‐differentiated cells and expression was absent in poorly differentiated tumour cells. Most of the squamous cell carcinomas showed elastase‐positive cells in the tumour stroma and also within the tumour cell nests. SKALP may interfere with the proteoloytic activity of infiltrating inflammatory cells or with hitherto unknown proteinases from the tumour cells. We hypothesize that in squamous cell carcinoma progressive loss of SKALP expression could facilitate tumour spread.
In situ localization of type III and type IV collagen‐expressing cells in human diabetic nephropathy
Authors: Razzaque Mohammed S. , Koji Takehiko , Taguchi Takashi , Harada Takashi , Nakane Paul K. 
Published: June 2005

AbstractNodular intercapillary glomerulosclerosis is the most typical lesion of diabetic nephropathy (DN) and is characterized by increased extracellular matrix (ECM) and amorphous masses of mesangial matrix. The local exaggeration of these deposits results in the formation in the typical diabetic nodule. To clarify the composition of the ECM of sclerotic lesions in DN, we investigated the distribution of type III and type IV collagens and their mRNAs by immunohistochemistry and in situ hybridization, respectively. In normal renal tissues, there was no intraglomerular immunostaining for type III collagen, while strongly positive staining was found in the extraglomerular interstitum. Positive immunostaining for type IV collagen was also present in the mesangium, glomerular basement membrane (GBM), Bowman's capsule, and the vascular pole of the normal glomerulus. In DN, the nodular lesions were negative for type III collagen and strongly positive for type IV collagen. On the other hand, in the late stage of global sclerosis, both type III and type IV collagens were diffusely present in the sclerotic matrix. To determine the origins of these type III and type IV collagens in the sclerotic matrix, in situ hybridization was performed, utilizing thymine‐thymine (T‐T) dimerized synthetic oligonucleotides complementary to either proα(III) chain or pro α1 (IV) chain mRNAs as probes. The signals were detected by enzyme immunohistochemistry using an anti‐T‐T antibody. Intraglomerular cells (glomerular epithelial and mesangil cells) containing type III collagen mRNA were found in DN with sclerotic lesions, but not in normal glomeruli. At this stage of sclerosis, intraglomerular cells (mainly glomerular epithelial cells and infrequently mesangial cells) were positive for type IV collagen mRNA, but there were few positive cells in globally sclerotic glomeruli. This study provides evidence that both type III and type IV collagens are synthesized by intraglomerular cells during sclerosis and become significant constituents of the sclerotic matrix in DN.
p53 Expression, mutation, and allelic deletion in ovarian cancer
Authors: McManus D. T. , Yap E. P. H. , Maxwell P. , Russell S. E. H. , Toner P. G. , McGee J. O'D. 
Published: June 2005

AbstractThe aim of this investigation was to study the prevalence of p53 gene mutations and allelic deletions in ovarian cancer and the relationship between these events and p53 expression. Genomic p53 was amplified by the polymerase chain reaction (PCR) from paraffin‐embedded sections of tumour and non‐tumour tissue. Exons 5–9 were screened for mutations using non‐isotopic single‐strand conformation polymorphism (SSCP) analysis. Allelic deletions at a sequence polymorphism in exon 4 were studied for loss of heterozygosity (LOH) by restriction analysis and by SSCP. p53 expression was detected by immunohistochemistry with the p53 antibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a mucinous tumour of low malignant potential, showed mutations. There was a statistically significant correlation between p53 mutation and expression (P<0·01) but seven cases showed discordance. Of 18 informative cases, eight (44 per cent) demonstrated LOH. Mutations were identified in three of the informative cases, two of which also had LOH. The remaining case showed mutations in two amplicons. p53 dysfunction, as indicated by mutation, deletion, or increased expression, is common in ovarian cancer. There is an association between these molecular events but the exact mechanisms of p53 inactivation remain to be elucidated.
HLA‐DR antigen expression and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections
Authors: Ioachim‐Velogianni Elli , Stavropoulos Nickolaos E. , Kitsiou Evangelia , Stefanaki Stella , Agnantis Niki J. 
Published: June 2005

AbstractLymphocyte subpopulations (B cells, CD4, CD8), interleukin‐20 receptors (IL‐2), monocytes/macrophages (Leu M5), and HLA‐DR antigen expression were studied immunohistochemically on frozen sections from 38 bladder cancer specimens. T cells predominated over B cells in all tumours. CD4‐positive lymphocytes predominated over CD8 in the stroma (CD4/CD8: 1·35/1), while in epithelial tumour cells CD8 was the prominent subpopulation (CD8/CD4: 1·75/1). Aberrant HLA‐DR expression was found in 21·05 per cent of bladder tumours. A strong correlation between CD4 and CD8 population densities and macrophages with the other subpopulations was noticed. In HLA‐DR‐positive tumours, there was no correlation of the percentage of positive cells with CD4‐ and CD8‐positive lymphocyte populations. Various parameters including IL‐2 receptors, B cells, CD8‐ and CD4‐positive cells, and macrophages did not differ significantly between the groups of tumours expressing and not expressing HLA‐DR antigen. There were no statistically significant differences in the population densities of B cells, CD8‐ or CD4‐positive cells, IL‐2 receptor, monocytes/macrophages, and HLA‐DR antigen expression among various clinicopathological parameters, including growth pattern, histological grade and clinical stage or patient's age and sex. These findings suggest that in transitional cell carcinoma of the urinary bladder, HLA‐DR antigen expression is independent of lymphocyte subpopulations. It is therefore possible that HLA‐DR expression by tumour cells reflect the existence of separate HLA‐DR‐positive or HLA‐DR‐negative tumour clones.
Proliferative activity in benign and neoplastic prostatic epithelium
Authors: Limas Catherine , Frizelle Sandra P. 
Published: June 2005

AbstractThe increasing availability of means for the early detection of prostatic cancer has brought under scrutiny the criteria used for prognosis and emphasized our limitations in understanding what determines the rate of progression in these cancers. The rate of cancer cell proliferation has been under intense investigation, which, however, has yielded conflicting results. In this study we evaluated the proliferative activity of benign and neoplastic prostatic epithelium, using various existing methodologies. We first analysed the variability introduced by the methodological approach and then attempted to demonstrate whether determination of the proliferative capacity had any clinical consequence that complemented the histological grading. Tissue samples from patients, 88 with cancer and 46 with benign prostatic pathology, were studied using in vitro bromodeoxyuridine (BrdU) incorporation as well as Ki67 and the proliferating cell nuclear antigen (PCNA) to estimate the proliferative activity. Increased proliferation was found consistently in inflammation and metaplasia, but not in hyperplasia. In contrast, cancers showed marked variability. Although average proliferation indices increased with grade, there was a wide scatter of values. Correlation was stronger with stage, but also depended on the methodology. Bromodeoxyuridine indices over 10 per mille had a positive predictive value of 79 per cent for cancers extending beyond the prostatic capsule and may prove particularly helpful for evaluating patients with grade 7 cancer. This observation is significant, since grade 7 cancers are the most frequent and the least predictable.
Possible role of tissue‐bound calcium ions in citrate‐mediated high‐temperature antigen retrieval
Authors: Morgan J. M. , Navabi H. , Schmid K. W. , Jasani B. 
Published: June 2005

AbstractHigh‐temperature preheating of sections in the presence of a salt (e.g., citrate) or a protein denaturant (e.g., urea) solution has been shown recently to provide a reliable alternative to tissue proteolysis for antigen retrieval from formaldehyde‐fixed, paraffin‐embedded tissues. However, the underlying mechanism of action of this form of pretreatment remains highly speculative. In this study, we show that calcium chelating agents such EDTA and EGTA are more effective than citrate in the retrieval of a citrate‐sensitive nuclear antigen, Ki‐67. Also, sodium carbonate and another calcium precipitating agent are both able to effect antigen retrieval at high temperatures. The overall data therefore suggest that either the chelation or the precipitation of tissue‐bound calcium ions, and perhaps also other divalent metal cations, is a critical step in salt‐mediated antigen retrieval. As a corollary, it is suggested that tight complexing of calcium ions or other divalent metal cations with proteins during formaldehyde tissue fixation is responsible for the masking of certain antigens.
Molecular mechanisms of drug resistance in tumours
Authors: Harrison David J. 
Published: June 2005

AbstractDespite advances in the design and use of chemotherapeutic drugs, the majority of human cancers are resistant to therapy at presentation or become resistant after an initial partial response. This suggests that resistance may be inherent in a tumour cell or may evolve under the selection pressure of drug administration. A number of possible molecular explanations for drug resistance exist. There may be exclusion of drug from the cell, failure to activate the prodrug to its active form, increased detoxification, alteration in the drug target, enahanced repair capability of the cell after injury, or failure to engage an appropriate response, leading to apoptosis in the damaged cell. Many of these factors may co‐exist in vivo in human tumours; some are a feature of cell lineage whilst others appear de novo during disease progression. Modulation of these mechanisms has been of some value in laboratory studies but widespread clinical application and benefit remain some way off.
Differentiation of a human rhabdomyosarcoma cell line after antineoplastic drug treatment
Authors: Melguizo C. , Prados J. , Aneiros J. , Fernandez J. E. , Velez C. , Aranega A. 
Published: June 2005

AbstractThe feasibility of treating solid tumours with differentiation therapy using antineoplastic drugs is currently being investigated, but the emergence of multidrug resistance remains the major limitation to this therapeutic approach. A rhabdomyosarcoma cell line resistant to actinomycin D (RD‐DAC) has been used as an in vitro model to investigate, with light and electron microscopy, the degree of differentiation in multidrug‐resistant cells. The parental cell line (RD), derived from a human embryonic‐type rhabdomyosarcoma, is undifferentiated, with no evidence of specific ultrastructural markers. Examination of resistant cells by transmission electron microscopy revealed myofilaments arranged parallel to the long axis of the cell, which was considered clear evidence of myogenic differentiation. These observations suggest that actinomycin D, the drug of choice in the treatment of rhabdomyosarcoma, induces differentiation in the cell line RD. It is postulated that multidrug resistance can interfere with cellular differentiation.
mdm2 gene alterations and mdm2 protein expression in breast carcinomas
Authors: Marchetti Antonio , Buttitta Fiamma , Girlando Salvatore , Palma Paolo Dalla , Pellegrini Silvia , Fina Paolo , Doglioni Claudio , Bevilacqua Generoso , Barbareschi Mattia 
Published: June 2005

AbstractThis study investigates the mdm2 gene status and expression in 66 surgically resected human breast carcinomas, with correlations with clinico‐pathological and biological data (histological type, grading, steroid receptor status, p53 expression, proliferative activity). Four (7.7 per cent) out of 52 informative cases bear mdm2 gene amplification (four‐ to ten‐fold) and 8 (15.4 per cent) of 52 cases showed borderline amplification (three‐fold). Nine (13.6 per cent) out of 66 cases showed strong mdm2 nuclear immunoreactivity. Twenty‐seven (40.9 per cent) cases showed isolated mdm2 reactive nuclei. All cases with clear amplification showed a high percentage of mdm2 immunoreactive nuclei. The relationship between gene amplification and mdm2 protein expression is highly significant (P<0.0001). No association was observed between mdm2 gene amplification and any of the considered clinico‐pathological and biological parameters, while mdm2 immunoreactivity showed a significant association only with oestrogen receptor immunoreactivity (P=0.009). p53 expression was associated neither with mdm2 gene amplification nor with mdm2 immunoreactivity. It could be tempting to hypothesize that the evaluation of the combined mdm2/p53 immunohistochemical phenotype in human breast carcinoma could give us better prognostic information than the evaluation of the expression of the p53 protein alone.
Epstein‐Barr virus association with early cancers found together with gastric medullary carcinomas demonstrating lymphoid infiltration
Authors: Takano Yasuo , Kato Yo 
Published: June 2005

AbstractSeven early gastric cancers obtained from patients also demonstrating Epstein‐Barr virus (EBV)‐positive gastric medullary carcinoma with lymphoid infiltration were investigated using a combined polymerase chain reaction (PCR) and in situ hybridization (ISH) approach. Sharing the same background mucosa as gastric medullary cancers, they comprised four intramucosal carcinomas, predominantly well‐differentiated adenocarcinomas, and three submucosal carcinomas, histologically showing mixtures of well and poorly differentiated adenocarcinoma. In the three cases of submucosal carcinoma, the presence of EBV was proven by means of both PCR and ISH. However, not all cancer cells were positive for EBV on the basis of ISH examination, in contrast to the large series of gastric carcinoma with lymphoid infiltration previously investigated. All four mucosal carcinomas were EBV‐negative. Lymphocyte‐determined membrane antigen (LYDMA) monoclonality, performed by PCR, and latent membrane protein‐1 (LMP‐1) and Epstein‐Barr virus (EBNA2) expression, assessed immunohistochemically, were negative in all seven cases. The results suggest that EBV becomes associated with gastric medullary carcinoma with lymphoid infiltration (GMCL) at a relatively early stage of the disease, shortly after the tumour has initially progressed to an invasive form, and plays some role in the manifestation as GMCL.
Expression of VE (vascular endothelial)‐cadherin and other endothelial‐specific markers in haemangiomas
Authors: Martìn‐padura Inés , de Castellarnau Conxita , Uccini Stefania , Pilozzi Emanuela , Natali Pier Giorgio , Nicotra Maria Rita , Ughi Francesca , Azzolini Cesare , Dejana Elisabetta , Ruco Luigi 
Published: June 2005

AbstractHaemangiomas are vascular tumours characterized by rapid growth and increased endothelial turnover. VE‐cadherin is a recently discovered endothelial cell‐specific cadherin located at intercellular junctions. In different types of epithelial tumours, cadherin expression is inversely correlated with invasiveness and metastatic dissemination. In this immunohistochemical study, VE‐cadherin expression has been analysed in different types of haemangioma. VE‐cadherin is highly expressed in endothelial cells of haemangiomas and is decreased, but still detectable, in some cases of haemangionendothelioma and angionsarcoma. The antigenic profile of most haemangioma cells was similar to that of normal endothelium. CD31, CD34, ICAM‐1, von Willebrand factor, and VLA integrins were expressed in haemangioma endothelium; in addition, the major components of vascular basement membrane, namely fibronectin, collagen type IV, and laminin, were correctly expressed and organized. Surprisingly, a marked reactivity for the M form of laminin (merosin) was detected in the basement membranes of two juvenile capillary haemangiomas. Overall, this study shows that, with the exception of angiosarcoma and haemangionendothelioma, vascular tumours maintain most of the differentiation characteristics of normal endothelium. This encourages speculation that in these pathologies, abnormal endothelial proliferation is more related to the release of local factors than to an altered endothelial phenotype.
Ductular structures in acute hepatitis with panacinar necrosis
Authors: Delladetsima Johanna K. , Kyriakou Vasiliki , Vafiadis Irene , Karakitsos Petros , Smyrnoff Tatiana , Tassopoulos Nikolaos C. 
Published: June 2005

AbstractThe development of ductular structures in acute hepatitis with panacinar necrosis was studied in 15 cases of fulminant hepatitis with variable clinical duration, using immunohistochemical markers. The immunophenotype of ductular structures was assessed by the expression of two bile duct epithelium determinants, wide spectrum cytokeratin and epithelial membrane antigen (EMA), and by their glycoconjugate expression using the specific binding lectins Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA). Ductular structures showed a predilective, but not a strictly selective location in acinar zone 1 and at the periphery of newly formed parenchymal nodules. All were positive for keratin, while EMA and the lectins were identified less frequently. Cytokeratin expression was additionally observed in hepatic cells with no other phenotypic alteration: this occurred along isolated hepatic cords, within parenchymal remnants, in the spared parenchyma in acinar zone 1 and occasionally at the periphery of parenchymal nodules. The presence of cytokeratin expression in liver cell plates in association with intermediate morphological stages of tubular remodelling speaks in favour of biliary metaplasia of hepatocytes. This process may represent a phenotypic‐functional accommodation of hepatocytes to an altered microenvironment, due to loss of parenchymal integrity. During the phenotypic shift, altered cytokeratin expression appears as one of the earliest biliary features, while EMA and the expression of glycoconjugates represent maturation markers.
An improved method for the species‐specific assessment of mycobacteria in routinely formalin‐fixed and paraffin‐embedded tissues
Authors: Richter Elvira , Schlüter Carsten , Duchrow Michael , Hahn Margrit , Rüsch‐Gerdes Sabine , Galle Jürgen , Flad Hans‐D. , Gerdes Johannes 
Published: June 2005

AbstractA polymerase chain reaction (PCR) assay for the rapid and species‐specific diagnosis of mycobacterial infections in paraffin‐embedded clinical specimens was developed using oligonucleotide primers to amplify a fragment of the DNA coding for the ribosomal 16S RNA of mycobacteria. The oligonucleotide primers amplified DNA from all 14 species of mycobacteria tested. By means of a reamplification protocol, as few as one to two mycobacteria could be detected in the presence of human DNA. The method of DNA isolation and amplification was applied on sections of routinely formalin‐fixed and paraffin‐embedded tissues. PCR for the β‐actin gene served as a control for successful DNA isolation. Mycobacterial DNA could be detected in cases of mycobacterial infections. The mycobacterial species was determined by additional sequencing of the PCR fragment. This PCR method may be a powerful tool for the diagnosis of mycobacterial infections from histopathological material and for the assessment of those mycobacteria that cannot readily be cultured, such as Mycobacterium leprae.