ISSN:0022-3417    

DOI:10.1002/path.1711770302

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractA series of 392 female breast carcinomas was analysed immunohistochemically for expression of p53 protein with special emphasis on the role of p53 as an independent prognostic factor. Altogether, 54·8 per cent of the carcinomas expressed p53 protein, with the mean [standard error (SE)] fraction of positive nuclei being 17·1 per cent (1·2 per cent). Expression of p53 protein was independent of tumour metastasis at diagnosis, axillary lymph node status, tumour diameter, histological type, tubule formation, proportion of intraductal growth, margin formation, necrosis, DNA ploidy, and S‐phase fraction. A high fraction of p53‐positive nuclei was significantly related to patient age under 70 years, high grade, severe nuclear pleomorphism, dense infiltration of tumour by lymphocytes, high mitotic index, and high apoptotic index (for all,P<0·05). Impaired survival probability in the entire cohort (P=0·05) and in the axillary lymph node‐positive (ANP) tumours (P=0·015) was associated with a fraction of p53‐positive nuclei less than 25 per cent, while in the axillary lymph node‐negative (ANN) tumours, expression of p53 had no prognostic value. In multivariate analysis, independent prognostic predictors included axillary lymph node status, tumour diameter, and mitotic index. In the ANN tumours, tumour diameter, fraction of p53‐positive nuclei, and tumour grade were independent prognostic factors, whereas in the ANP tumours, diameter and mitotic index were the two independent prognostic factors. The results suggest that abnormal expression of p53 protein is only a weak independent prognostic factor in fem

ISSN:0022-3417    

DOI:10.1002/path.1711770303

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractEpstein–Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma‐like carcinomas (LELC) of foregut‐derived organs. Recently this group of EBV‐associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach.In situhybridization (ISH) using a sensitive digoxigenin‐labelled EBER RNA probe was performed on 167 consecutive unselected primary non‐small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5·4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of the EBER‐positive tumours showed patchy expression of the viral latent membrane protein (LMP‐1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positive tumours were LELC, whereas no conventional type of non‐small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8:1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow‐up periods of 23–52 months. Southern blot analysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV‐associated lung tumours justify their consideration as a distinct cl

ISSN:0022-3417    

DOI:10.1002/path.1711770304

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThebcl‐2 proto‐oncogene, which inhibits programmed cell death (apoptosis), has recently been found to be cyclically expressed in human endometrium. In order to investigate its role in endometrial hyperlasia and neoplasia,bcl‐2 expression was studied in 25 cases of endometrial carcinoma and 20 cases of endometrial hyperplasia (eight simple, two complex, and ten atypical hyperplasias). Uniform intense cytoplasmicbcl‐2 expression was found in all cases of non‐atypical hyperplasia, and less strong positivity in eight out of ten cases of atypical hyperplasia. In well‐differentiated carcinomas, nine out of ten showed weak to moderatebcl‐2 expression, whereas six out of seven poorly differentiated carcinomas werebcl‐2‐negative. Moderately differentiated tumours were an intermediate group, with six out of eight being positive. Widespread localization ofbcl‐2 protein to the chromosomes of dividing cells was also demonstrated, regardless of cytoplasmicbcl‐2 expression, with rare staining of interphase nuclei. Our findings suggest a role forbcl‐2 in the natural history of endometrial neoplasia and studies are needed to determine its usefulness as a prognostic marker. The finding ofbcl‐2 localization to chromosomes has important implications for it

ISSN:0022-3417    

DOI:10.1002/path.1711770305

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractExpression ofbcl‐2 is associated with inhibition of apoptosis and extension of cell survival. The importance of apoptosis in relation to the development and progression of renal cell neoplasia remains undefined so far. In order to determine the expression ofbcl‐2 oncoprotein in normal and neoplastic renal cells, 37 renal tumours were investigated by immunolabelling, including 13 clear cell carcinomas, ten tubulopapillary carcinomas, four chromophobic renal cell carcinomas, and ten oncocytomas. Twenty‐six samples of adjacent normal renal tissue served as controls.bcl‐2 expression was correlated with cell proliferation activity as estimated by Ki67 antigen expression, and p53 protein expression in the tumour samples. The results demonstrate that in the normal kidney, positivebcl‐2 immunostaining was present in glomerular parietal epithelial cells, in distal tubular cells, and in sparse proximal tubule cells. Renal cell tumours showed heterogeneousbcl‐2 expression according to the tumour cell type. While the majority of carcinomas of clear cell type were usually negative or contained sparsely distributed positive cells, all tubulopapillary carcinomas were consistently positive forbcl‐2. In oncocytomas and chromophobic carcinomas, there was a low percentage ofbcl‐2 immunoreactive tumour cells; some nuclearbcl‐2 positivity was detected in one chromophobic tumour. These findings indicate variablebcl‐2 oncoprotein expression in different types of renal cell tumours, with the highest level of expression in tubulopapillary carcinomas. No clear relationship was found between nuclear grade, cell proliferation activity, and level ofbcl‐2 expression. p53 protein was detected in only one tubu

ISSN:0022-3417    

DOI:10.1002/path.1711770306

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe c‐kitproto‐oncogene product and its ligand stem cell factor play an important role in haematopoiesis, spermatogenesis, and melanogenesis. Using an anti‐c‐kitantiserum raised against a synthetic peptide, we studied the immunohistochemical expression of the c‐kitgene product in 60 germ cell tumours (GCTs) (53 testicular, 7 extragonadal), derived from primary GCTs in 45 cases and metastatic tumours in 15 cases. Twenty‐eight out of 28 seminomas showed c‐kitmembranous staining in the majority of cells. A similar pattern of expression was seen in intratubular germ cell neoplasia. Nine out of 29 (32 per cent) non‐seminomas displayed cytoplasmic, but not membranous, c‐kitimmunoreactivity in occasional cells. In three mixed GCTs, c‐kitexpression was limited to the seminoma component. In normal testis, c‐kitexpression was observed in some basal tubular cells, corresponding to undifferentiated spermatogonia. These results suggest a role for c‐kitin the oncogenesis of GCT, where down‐regulation of c‐kitmight be a critical step during progression from seminomas to non‐seminomas. Immunohistochemical analysis of c‐kitshould be considered as a diagnostic aid for GCT and in particular may be helpful in the identification of

ISSN:0022-3417    

DOI:10.1002/path.1711770307

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractVascular endothelial growth factor (VEGF) is a dimeric glycoprotein that exerts a proliferative effect specifically on endothelial cells. VEGF can increase vascular permeability and collagenase activity, is chemotactic for monocytes, and may dilate blood vessels. It can be induced by phorbol ester and cAMP in both mesenchymal and epithelial cells.In vitrocell culture experiments suggest that VEGF is upregulated by oxygen deprivation. In this study we tested whetherin vivoacute and/or chronic reduction of renal blood flow by vascular obstruction would result in increased expression of VEGF mRNA and protein. Three normal kidneys, five human kidneys with narrowing of preglomerular vessels by vascular rejection or by vasculitis, and eight kidneys with nephrosclerosis and/or diabetic nephropathy were examined.In situhybridization with35S‐labelled riboprobes showed a pronounced expression of VEGF mRNA in acutely hypoxic proximal and distal tubules of both the cortex and medulla; VEGF protein was demonstrated in the epithelia of these tubules by immunohistochemistry. In kidneys with chronically reduced blood flow, the majority of atrophic tubules were negative for VEGF mRNA and protein, although interstitial cells expressed VEGF mRNA. In arcuate arteries showing intimal and adventitial fibrosis, some medial smooth muscle cells were positive for VEGF mRNA. In glomeruli with segmental sclerosis, viable podocytes showed a prominent signal for VEGF mRNA. Mesangial cells did not express VEGF in the cases studied. It is possible that hypoxia itself led to the upregulation of VEGF in tubular epithelia and vascular smooth muscle cells. The vasodilatory and permeability‐promoting effects of the endothelial growth factor produced by damaged tubular epithelia may constitute a mechanism to alleviate a decrease in blood flow and substrate availability and to re‐establish vascular inte

ISSN:0022-3417    

DOI:10.1002/path.1711770308

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe histological and ultrastructural changes of mesangiocapillary glomerulonephritis (MCGN) are not unique to this entity: splitting of basement membrane (BM) is seen in a number of conditions with an altered coagulation pattern. The distribution of endothelial cells in the glomerular capillaries in five cases of MCGN was studied by light and electron microscopy and immunocytochemistry; endothelial cells were stained with peroxidase or FITC‐conjugated antibodies against Factor VIII‐related antigen or CD34 antigen and observed with conventional light/immunofluorescence microscopy and confocal laser scanning microscopy for three‐dimensional reconstruction. Electron microscopy was performed with colloidal gold labelling. Endothelial cells were shown to be present within the duplicated basement membranes of capillaries and continuity was demonstrated with endothelial cells lining the capillary lumina. These results suggest that endothelial cells as well as mesangial cells can participate in the formation of the characteristic double contour of capillary walls in MCGN, especially in the early stages. There are some similarities to the changes seen in larger arteries as a consequence of thrombotic di

ISSN:0022-3417    

DOI:10.1002/path.1711770309

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn some studies of breast cancer, quantitation of immunohistochemically highlighted microvessel ‘hot spots’ has been shown to be a powerful prognostic tool. However, the antibody used, the number and size of the ‘hot spots’ assessed, and the stratification of patients into high and low vascular groups vary between studies. Furthermore, little is known about the relationship between microvessel density and other vascular parameters. These uncertainties and the laborious nature of the technique make it unsuitable for diagnostic practice. Both manual and computerized image analysis techniques were used in this study to examine the relationship between microvessel density and the vascular parameters in different sized microscopic fields in a pilot series of 30 invasive breast carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley point counting, and observer subjective vascular grading were also assessed as more rapid methods of measuring tumour vascularity. A Chalkley count was also performed on a further 211 invasive breast carcinomas. Significant correlations were observed between manual microvessel density and luminal perimeter (r=0·6,P=0·0004), luminal area (r=0·56,P=0·002), and microvessel number (r=0·57,P=0·0009) by computerized analysis. There were also significant correlations between the microscopic hot spots of 0·155 mm2and 0.848 mm2for microvessel number (r=0·81,P>0·00005), luminal perimeter (r=0·78,P<0·00005), and luminal area (r=0·65,P=0·0001). In addition, a significant correlation was observed between microvessel density and both subjective vascular grade (P=0·002) and Chalkley count (P=0·0001). A significant reduction in overall survival was observed between patients stratified by Chalkley count in both a univariate (P=0·02) and a multivariate (P=0·05) analysis in the 211 invasive breast carcinomas. These findings show that Chalkley counting is a rapid method of quantifying tumour angiogenesis and gives independent prognostic information which might be usefu

ISSN:0022-3417    

DOI:10.1002/path.1711770310

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractImmunocytochemical studies examining the Ki‐67 proliferation marker in paraffin‐embedded material have recently been made possible by the availability of several antibodies, notably MIB‐1, which are readily applicable to microwaved sections. Using breast cancer material, the present study examines correlations shown by these new paraffin assays and also by PCNA (proliferating cell nuclear antigen), an existing marker of proliferation, with the established Ki‐67 cryosection assay. Paraffin sections were microwaved prior to incubation with Ki‐67 or MIB‐1 antibodies. Signal detection was carried out with a biotinylated secondary antibody, peroxidase‐conjugated streptavidin, and DAB/H2O2chromogen. The results suggest that caution is required when studying proliferation in paraffin‐embedded breast cancers by immunostaining using Ki‐67 antibodies. Nuclear staining in wax sections (Ki‐Par, MIB‐1, PCNA) greatly exceeded that in cryosections (Ki‐Froz) and thus correlations were notably absent between Ki‐Par or PCNA immunostaining and the routine Ki‐Froz assay. Immunostaining with MIB‐1 or PCNA may, however, be useful to assess proliferation if cut‐offs are applied to eliminate weak immunostaining associated with wax sections. Thus, an approximately linear relationship was seen between MIB‐1/Ki‐Froz, which was improved if only moderately or moderately/strongly MIB‐1‐positive cells were scored. Similarly, a significant correlation was also revealed between PCN

ISSN:0022-3417    

DOI:10.1002/path.1711770311

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY