bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of immunohistochemical detection of ERBB2 in human breast cancer: Impact of fixation
Authors: Penault‐Llorca Frédérique , Adelaïde José , Houvenaeghel Gilles , Hassoun Jacques , Birnbaum Daniel , Jacquemier Jocelyne 
Published: June 2005

AbstractIn an attempt to standardize the immunohistochemical detection of ERBB2, we evaluated six normal breast samples and 58 breast carcinomas for (1) the effect of four different fixatives (Bouin's fluid, buffered formalin, alcoholic formalin, and methacarn), and (2) the sensitivity and specificity of eight commercially available antibodies. ERBB2 gene copy numbers and RNA transcripts were measured by Southern and Northern blot analysis in all samples. The BT‐474 and MCF7 cell lines were processed in the same way as the tissue samples and used as references of activation or the normal state of the ERBB2 gene, respectively. Complete concordance between immunohistochemistry and molecular biology was observed in 43/58 cases (74 per cent). However, fixation and processing protocols significantly affected the reactivity of the antigenic determinants. The most consistent results were obtained with NCLCB11 on frozen sections and with Tab250 on paraffin‐embedded sections. For prospective studies, the use of alcoholic formalin in association with a highly specific antibody (Tab250, 9G6, NCLCB11, or OA‐11‐854) gave the best results. Methacarn appears to be a reliable fixative, but was studied in only 28 cases. For retrospective studies, the most important parameter to take into account is the sensitivity of the antibody. Thus, with Bcuin s fixation, 3B5 was the only reliable antibody, whereas with buffered formalin, Tab250 gave the most consistent results. This study will help inter‐laboratory comparisons, and in determining the prognostic significance of ERBB2 expression in breast carcinomas using a standardized methodology.
Epstein‐Barr virus in nasal T‐cell lymphomas (polymorphic reticulosis/midline malignant reticulosis) in Western China
Authors: Van Gorp Joost , Weiping Liu , Jacobse Karen , Yong‐Huei Liu , Feng‐Yuan Li , de Weger Roel A. , Li Gandi 
Published: June 2005

AbstractPolymorphic reticulosis (PR) or midline malignant reticulosis (MMR) is considered to be malignant, or at least pre‐malignant T‐cell proliferations of the nose or midline area. Recent reports of small series of nasal T‐cell lymphomas have shown a strong association with Epstein‐Barr virus (EBV). Furthermore, a peculiar phenotype is described, with expression of CD56 and not of CD3, suggesting a possible origin from natural killer (NK) cells. We have analysed a series of 38 cases of PR/MMR for the presence of EBV by in situ hybridization (ISH) of the EBV‐encoded RNAs 1 and 2 (EBER). Twenty cases were tested for expression of EBV‐encoded latent membrane protein 1 (LMP‐1). Special attention was also paid to the expression of CD3 and the NK cell‐related marker CD56. Thirty‐two cases (84 per cent) showed positive EBER ISH. In 5 of 20 cases, LMP‐1 expression was detected. In three cases, a few scattered cells were positive, and in two cases, LMP‐1 was detected in clusters of atypical cell. Most of the neoplasms showed expression of CD3 (89 per cent) and in 27 cases (71 per cent), CD56 was detected. These results are consistent with an aetiopathogenetic role for EBV in most, but not all, cases of PR/MMR. Our findings are less supportive of a major role for LMP‐1 in tumour genesis. CD3 expression in most of the cases of PR/MMR underlines the T‐cell origin of these neoplasms, often with aberrant expression of CD56.
Expression of the trefoil peptides pS2 and human spasmolytic polypeptide (hSP) in Barrett's metaplasia and the native oesophageal epithelium: Delineation of epithelial phenotype
Authors: Hanby Andrew M. , Jankowski Janusz A. Z. , Elia George , Poulsom Richard , Wright Nicholas A. 
Published: June 2005

AbstractThe distribution of the two trefoil peptides pS2 and human spasmolytic polypeptide (hSP) and their mRNAs was investigated in 90 selected oesophageal biopsies, 23 of which contained epithelium with wholly gastric cardiac‐type morphology, 52 specialized (intestinal)‐type metaplasia, and 15 non‐metaplastic oesophageal epithelium. No fundic‐type epithelium was represented. The cardiac‐type epithelium resembled true gastric antral epithelium, with hSP and pS2 mRNA localization to the superficial/foveolar compartment and hSP mRNA alone in deeper glands. The pattern of peptide distribution was broadly in line with the mRNA, but hSP peptide was generally not demonstrable in the surface epithelium. pS2 immunostaining was diffusely cytoplasmic, whereas in specialized‐type mucosa it was aggregated and cytoplasmic hSP mRNA was demonstrable in surface epithelium of incomplete‐ but not complete‐type intestinal (specialized) metaplasia. Deep glands with morphological features of pyloric glands/ulcer‐associated cell lineage (UACL) typically contained only hSP peptide and its mRNA. In three biopsies containing specialized epithelium, small foci morphologically identical to true small intestinal surface epithelium were seen in which only pS2 mRNA and peptide were found and then only in rare goblet cells. Neither squamous epithelium nor oesophageal glands contained demonstrable pS2/hSP mRNA or peptide. The function of these proteins in the metaplastic mucosa of Barrett's oesophagus is unknown but they may reflect an epithelium responding to repeated insult. Their localization facilitates definition of the disparate epithelium types seen in this portion of the gut, with both native gastric and intestinal epithelia, and may help to pinpoint high‐risk epithelium in Barrett's oesophagus, a potentially preneoplastic condition.
DNA in situ hybridization as a diagnostic tool in the discrimination of melanoma and spitz naevus
Authors: de wit Peter E. J. , Kerstens Harold M. J. , Poddighe Pino J. , Van Muijen Goos N. P. , Ruiter Dirk J. 
Published: June 2005

AbstractAs the clinical and histological differential diagnosis between Spitz naevus and cutaneous melanoma may be very difficult, we have investigated whether DNA in situ hybridization may be helpful in resolving this problem. To this end, routinely‐processed paraffin sections of 15 typical Spitz naevi, 15 typical nodular melanomas, and five cases originally misdiagnosed as Spitz naevi but which later metastasized and were reclassified as melanoma were analysed using a method previously described (De Wit et al., J Invest Dermatol 1992; 98: 450–458). Microscopical semi‐quantitative evaluation revealed that the number of nuclei with supernumerary aberrations of the centromere region of chromosome 1, suggestive of aneuploidy, was significantly different in Spitz naevi and nodular melanoma. The mean number of aberrant nuclei per high power field was 0.41 and 4.01, respectively (P=0.0001). On applying the results of the typical lesions to the equivocal, originally misdiagnosed lesions, three out of five could be identified as melanoma. These results suggest that the application of DNA in situ hybridization may contribute to the positive identification of histologically equivocal pigmented lesions. The advantages of this technique are that it is cheap, requires little tissue, and can be applied on routinely‐processed paraffin sections.
Borrelia burgdorferi‐induced ultrastructural alterations in human phacgocytes: A clue to pathogenicity?
Authors: Riting Michael G. , Häpl Thomas , Krause Andreas , Kressel Michael , Groscurth Peter , Burmester Gerd R. 
Published: June 2005

AbstractA chronic infection with the spirochaete Borrelia burgdorferi typically results in a multistage, multistem illness. Thus, Lyme borreliosis may provide an interesting model to study the pathomechanisms of microbial persistence. In the present investivation, human peripheral blood monocytes, polymorphonuclear leukocytes, and synovial macrophages were incubated with B. burgdorferi and examined by light and electron microscopy. It was found that incubation with the spirochaetes induced distinct features in the phagocytes. Features which may be related to the pathogenesis of Lyme disease included the segmental uptake of spirochates with leaky lysosomes, the invagination of large membrane areas, the extra‐lysosomal degradation of internalized B. burgdorferi cells and, finally, the formation of mononuclear synctial cells and homotypic cell clusters. Feautres of unknown relevance were the occurrence of two types of cytoplasmic inclusion bodies and exocytic vesicles. These novel findings suggest that reactive alterations of the phagocytes may contribute to the pathogenesis of Lyme borreliosis, which could help to focus future histopathological studies. Moreover, these results may provide new insights into the pathogenesis of other infectious diseases characterized similarly by microbial persistence.
The ulceration‐associated cell lineage (UACL) reiterates the Brunner's gland differentiation programme but acquires the proliferative organization of the gastric gland
Authors: Ahnen Dennis J. , Poulsom Richard , Stamp Gordon W. H. , Elia George , Pike Christine , Jeffery Rosemary , Longcroft Janet , Rio Marie‐Christine , Chambon Pierre , Wright Nicholas A. 
Published: June 2005

AbstractThe ulceration‐associated cell lineage (UACL) develops in the human gastrointestinal mucosa after ulceration; it grows out from the bases of adjacent crypts and ramifies in the lamina propria to form a new gland, finally giving rise to a duct by which the glandular secretion and indeed cells are carried to the surface. Using immunocytochemistry and in situ hybridization with 35S‐labelled riboprobes, we have defined the pattern of trefoil peptide gene expression (pS2; human spasmolytic polypeptide, hSP), epidermal growth factor/urogastrone (EGF/URO), and the distribution of cell proliferation during the development of the UACL, as indicated by immunostaining for proliferating cell nuclear antigen (PCNA). Our studies reveal that the morphogenesis of the UACL shows a marked morphological resemblance to developing Brunner's glands; the pattern of trefoil peptide gene expression during UACL development is also very similar. However; trefoil peptide gene expression in the mature UACL complex is unique amongst gastrointestinal cells. The mature UACL shows a distinctive proliferative organization: while the early buds and glands are non‐proliferative, apparently being fed by cells from the parent crypts, a definitive proliferative zone develops within the duct. This, of course, corresponds to the location of the gastric gland proliferative zone. We propose that while the UACL shows novel features, it shares its differentiation programme with Brunner's glands, but its pattern of cell renewal eventually is that of the gastric gland.
Expression of pS2 protein in transitional cell bladder tumours
Authors: Lipponen P. K. , Eskelinen M. J. 
Published: June 2005

AbstractA series of 201 bladder cancer biopsy specimens was analysed immunohistochemically for the expression of pS2 protein. Altogether, 61 per cent of the tumours were pS2‐negative; in 16 per cent less than 1 per cent and in 23 per cent of cases more than 1 per cent of cells were pS2‐positive. Normal transitional epithelium was negative for pS2. The fraction of positive cells was higher in poorly differentiated non‐papillary tumours and in invasive tumours with pelvic lymph‐node (P=0.05) and distant metastasis (P=0.10). pS2 expression was not related to sex, while patients aged 60–70 years had low fractions of pS2‐positive cells (P=0.03). DNA ploidy, S‐phase fraction, mitotic index, morphometric nuclear features, and expression of c‐erbB‐2, p53, and epidermal growth factor receptor were independent of expression of pS2. Tumours expressing pS2 in over 10 per cent of cells had a lower survival probability (P=0.0486). The results show that pS2 is expressed in 40 per cent of transitional cell bladder tumours, but that this marker has no clinical significance over established prognostic factors.
Site of production of IGF1 in the normal and stimulated mouse thyroid
Authors: Thomas Geraldine A. , Davies Howard G. , Williams E. Dillwyn 
Published: June 2005

AbstractInsulin‐like growth factor 1 (IGF1) has emerged as an essential factor in the follicular cell growth response in vitro to TSH, although its source within the thyroid in vivo is not clear. We have studied the localisation of IGF1 mRNA by in situ hybridization using digoxigenin labelled oligoprobes in tissue sections of mouse thyroid. Our results show that in the thyroid IGF1 mRNA is predominantly present in follicular cells and C cells rather than the stroma. Follicular cell levels are higher during postnatal thyroid growth and during the growth response to goitrogen administration, but decrease in the mature animal. This decrease in production is limited to the follicular cells, as IGF1 mRNA is still easily demonstrable in C cells and in the parathyroid. Immunocytochemistry for IGF1 peptide shows a weak and variable follicular cell content in both juvenile and mature mice, but a more uniform distribution during growth in response to a goitrogenic stimulus. These studies show that the follicular cells are the main source of IGF1 in the thyroid, and suggest that the role of IGF1 in follicular cell growth is as an autocrine factor.
Brief, high‐temperature heat denaturation (pressure cooking): A simple and effective method of antigen retrieval for routinely processed tissues
Authors: Norton Andrew J. , Jordan Suzanne , Yeomans Patricia 
Published: June 2005

AbstractThe merits of microwave‐based antigen retrieval methods for diagnostic immunohistochemistry have recently been emphasized. As such technology has drawbacks for busy routine laboratories, we have investigated an alternative method of heat‐mediated antigen retrieval (HMAR), using a domestic pressure cooker as a source of superheating. A simple protocol, with superheating in 0.01 M citrate buffer (pH 6.0) for 2 min, gave results comparable to those obtainable in a microwave oven. The range of antigens retrieved and the antigens for which heating was ineffective matched the published microwave experience. The advantages included the speed of treatment, the reproducibility of results with large batches of slides, the ability to use metal slide racks, and economy of time and equipment costs.
Human non‐small cell lung cancer: P53 protein accumulation is an early event and persists during metastatic progression
Authors: Fontanini Gabriella , Vignati Silvana , Bigini Daniela , Basolo Fulvio , Pingitore Raffaele , Bevilacqua Generoso , Merlo Giorgio R. , Ribecchini Alessandro , Angeletti Carlo Alberto 
Published: June 2005

AbstractMutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non‐small cell lung cancer (NSCLC). Little is known, however, about the timing of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic leisons, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non‐invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.
Testicular germ cell tumours of childhood in Denmark, 1943‐1989: Incidence and evaluation of histology using immunohistochemical techniques
Authors: Visfeldt Jakob , Jørgensen Niels , Müler Jørn , SkakkebæK Niels E. , Møller Henrik 
Published: June 2005

AbstractIn the Danish Cancer Registry, 72 testicular tumours in boys younger than 15 years of age were recorded during the period 1943‐1989 and material from 34 of these was retrieved from Danish departments of pathology. The histological types were evaluated and the role of immunohistochemical staining was analysed. The survival of the patients was correlated with the histological diagnoses, and changes in the incidence of testicular cancers in childhood were analysed. Twenty‐nine of the 34 patients had germ cell tumours, which fell into two groups (infantile and pubertal) with distinct differences. The tumours of infancy usually presented before the age of 3 years and were either pure yolk sac tumours or teratomas. The tumours of puberty showed no morphological or immunohistochemical differences from adult germ cell tumours. In the infantile group, immunohistochemical staining confirmed the morphological evaluation but was not necessary for diagnosis. Patients in the infantile group seemed to have a better prognosis than adult patients, only one patient dying from his disease, whereas the pubertal patients seemed to have a prognosis similar to that of adult patients. The incidence of infantile testicular cancer in Denmark appears to have increased at almost the same rate as that observed in adult men, but due to the small numbers in infancy, this cannot be statistically substantiated. We conclude that the testicular germ cell tumours of infancy and puberty may arise from different precursor cells, but both groups seem to arise prenatally.
Decreased expression of cellular markers in Epstein‐Barr virus‐positive Hodgkin's disease
Authors: Bai M. C. , Jiwa N. M. , Horstman A. , Vos W. , Kluin PH. H. , Valk P. Van Der , Mullink H. , Walboomers J. M. M. , Meijer C. J. L. M. 
Published: June 2005

AbstractEpstein‐Barr virus (EBV) has been demonstrated in the Reed–Stenberg cells and their mononuclear variants (Hodgkin cells; H‐RS cells) in a substantial number of Hodgkin's disease (HD) cases. Moreover, EBV can modulate both in vivo and in vitro the expression of several cellular genes, including lymphoid differentiation markers. Therefore we investigated, in 64 cases of HD, the relationship between the presence of EBV and the expression of lymphoid (CD45RB), T‐ (CD3, CD45RO), B‐ (CD20, MB2 antigen, CDw75), and myeloid‐cell lineage markers (CD15), and of activation markers (CD30, EMA, and the 115D8 antigen) on the H‐RS cells. EBV‐positive cases, as demonstrated by the presence of EBER‐1 and ‐2 RNA and LMP‐1 protein expression, showed a significant reduction in the expression on H‐RS cells of T‐cell lineage (CD3, p<0·02), B‐cell lineage (CD20, P<0·005), AND ACTIVATION MARKERS (ema; P<0·002 and the 115D8 antigen; P<0·001) as compared with EBV‐negative cases. No differences were found in the expression of CD15, CD30, CD45RO, CD45RB CDw75, or the MB2 antigen on H‐RS cells in EBV‐positive and EBV‐negative HD cases. Interestingly, in 11 cases of EBV‐negative HD, B‐as well as T‐cell lineage markers could be found on some H‐RS cells. These data suggest that EBV in H‐RS cells is able to down‐regulate the expression of T‐ (CD3) and B‐ (CD20) cell lineage markers and lymphoid activation markers (EMA and the 115D8 antigen). For this reason, the origin of H‐RS cells in HD, as studies by immunohistochemistry, cannot be discussed without taking into account the presence of EBV.
Langerhans' cell histiocytosis cells are activated langerhans' cells
Authors: Emile Jean‐François , Fraitag Sylvie , Leborgne Michèle , de Prost Yves , Brousse Nicole 
Published: June 2005

AbstractLangerhans' cell histiocytosis (LCH) is characterized by the presence of large mononucleated cells, associated with inflammatory cells. The Langerhans' cell (LC) lineage of the mononucleated cells is suggested by the presence of Birbeck granules and the expression of CD1a. We investigated the presence of 14 markers expressed by normal LCs in vitro. Nine skin and one lymph node frozen biopsies of LCH children were analysed by in situ immunohistochemistry. The data were compared with six skin and five lymph node frozen biopsies. LCH cells of the ten samples were positivie for all 14 LC markers. We observed three different groups of markers, according to the respective staining of normal LCs and LCH cells. Group 1 included DR, DQ, CD1a, CD1c, and ICAM‐3. Markers of group 1 were present on the majority of both normal LCs and LCH cells. Group 2 included CD1b, CD4, LFA‐1, LFA‐3, CD32, and CD68. Markers of group 2 were detected on the majority of LCH cells, but only on a fraction of normal LCs. Group 3 included CD11b, CD24, and B7/BB1. Markers of this group were detected on LCH cells, but not on normal LCs. This in situ immunohistochemical study confirms that LCH cells belong to the LC lineage. The different clinical LCH syndromes had the same immunohistochemical staining. The expression of some markers of groups 2 and 3 is known to be related to the activation of LCs in vitro. Our study suggests that LCH cells are activated LCs.
Assessment of epidermal dendritic cell markers and T‐lymphocytes in psoriasis
Authors: Jones J. Louise , Berth‐Jones John , Fletcher Alan , Hutchinson Peter E. 
Published: June 2005

AbstractEpidermal dendritic and T‐cell counts have been performed in lesional and non‐lesional skin from 35 psoriatic patients. The aims were to investigate absolute changes and interrelationships between these cellular elements in psoriasis and to explain apparent discrepancies between these results and reports in the literature. In non‐lesional skin, the most frequently expressed dendritic cell marker was CD1a. HLA‐DR+ and α‐mannosidase+ dendritic cells were approximately 50 per cent and S100+ cells were 25 per cent as frequent. T‐lymphocytes were rare, CD4+ cells predominating. In lesional psoriatic epidermis, there was a definite increase (approximately two‐fold) in the absolute number of CD1a+ dendritic cells. This differs from the conclusions from the majority of previous studies. However, when cell counts were expressed per unit area of vertical section, there was a decrease in CD1a+ cells in lesional skin, which is an explanation for this discrepancy. There was a greater increase in absolute HLA‐DR+ cell counts, so that the numbers of cells expressing CD1a and HLA‐DR were similar in lesional skin. S100 expression increased proportionately with CD1a+, but there was no absolute increase in α‐mannosidase+ cells, which might represent a separate sub‐population of dendritic cells. The greatest cellular increase was in T‐lymphocytes, particularly CD8+. In lesional skin, direct correlations have been demonstrated between epidermal thickness, HLA‐DR+ dendritic cells and T‐lymphocytes, particularly CD8+ cells. We would suggest that the present method of quantification is of value for the analysis of absolute changes in epidermal infiltrates, particularly psoriasis, and could be applied to other epidermal pathologies.