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Showing papers in "The Journal of Pathology in 1990"


Journal ArticleDOI
TL;DR: Data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation, however, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost.
Abstract: Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression

1,441 citations


Journal ArticleDOI
TL;DR: The recent discovery that brain PGP 9.5 is a ubiquitin carboxyl‐terminal hydrolase suggests that the role of this protein should be studied in relation to ubiquitinated cellular inclusions characteristic of several chronic human degenerative diseases.
Abstract: The recent discovery that brain PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase suggests that the role of this protein should be studied in relation to ubiquitinated cellular inclusions characteristic of several chronic human degenerative diseases. Formalin-fixed, paraffin-processed sections known to contain ubiquitin-protein conjugate immunoreactivity in cortical Lewy bodies, neurofibrillary tangles, Rosenthal fibres, Pick bodies, spinal inclusions in motor neurone disease, and Mallory's hyaline in alcoholic liver disease were immunostained to localize PGP 9.5. The majority of cortical Lewy bodies in diffuse Lewy body disease showed immunoreactivity for PGP 9.5. In Alzheimer's disease, only a minority of loosely arranged globose-type neurofibrillary tangles were immunostained together with a minority of neurites surrounding senile plaques. In cerebellar astrocytomas, the periphery of the majority of Rosenthal fibers was immunostained in addition to strong diffuse cytoplasmic immunostaining in some astrocytes lacking apparent Rosenthal fibers. In Pick's disease, there was no immunostaining of inclusions but there was intense immunostaining of swollen Pick cells. No spinal inclusions in motor neurone disease were stained; however, anterior horn neurones appear to show increased levels of PGP 9.5 compared with those from control cases. No immunostaining of hepatic Mallory's hyaline was demonstrable, which accords with suggestions that PGP 9.5 is a tissue-specific ubiquitin C-terminal hydrolase isoenzyme. The differential detection of a ubiquitin C-terminal hydrolase in different forms of ubiquitinated inclusion body in the nervous system may form the basis of a method for assessment of the staging of inclusion body biogenesis and give insight into the dynamics of inclusion body formation.(ABSTRACT TRUNCATED AT 250 WORDS)

362 citations



Journal ArticleDOI

235 citations


Journal ArticleDOI
TL;DR: It is reported that pS2 and hSP expression occurs in a wide range of endodermally‐derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration.
Abstract: The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.

214 citations


Journal ArticleDOI
TL;DR: The nuclear: cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.
Abstract: This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3-independent, and expressed low degrees of anchorage independence (CFE less than 4 per cent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co-expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins (K1, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear:cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.

180 citations


Journal ArticleDOI
TL;DR: With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary.
Abstract: An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.

176 citations


Journal ArticleDOI
TL;DR: There is abnormal expression of c‐erbB‐2 oncogene in nearly 20 per cent of cases although mutational activation of this gene is not seen in human pancreatic adenocarcinoma.
Abstract: The c-erb B-2 oncogene encodes a 190 kD transmembrane growth factor receptor which is closely related to the EGF receptor and has been found to be amplified and overexpressed in a number of human adenocarcinomas, particularly of the breast. We have analysed, by immunocytochemistry using the 21N antibody, expression of c-erb B-2 in a retrospective series of pancreatic adenocarcinoma, chronic pancreatitis, and examples of histologically normal pancreas. In three cases (21 per cent) of chronic pancreatitis, there were focal areas of cytoplasmic immunoreactivity in regenerating epithelium. In 15 cases (17 per cent) of pancreatic adenocarcinoma, cytoplasmic immunoreactivity was seen, while in two cases (2 per cent) strong membrane staining of tumour cells was seen which could be blocked by peptide controls. c-erb B-2 immunoreactivity was also demonstrated using a second antibody, 20N, which recognizes another peptide sequence of the c-erb B-2 protein. There was no relationship between immunoreactivity and histological subtype or grade, but there was absolute concordance between staining in primary and metastatic deposits. Since the rat homologue (neu) of the c-erb B-2 oncogene may be activated by a specific point mutation in its transmembrane region, we have analysed 23 cases from this series for mutations by polymerase chain reaction amplification and sequence-specific oligonucleotide hybridization. We were unable to identify activity mutations in this series. These data suggest that there is abnormal expression of c-erb B-2 oncogene in nearly 20 per cent of cases although mutational activation of this gene is not seen in human pancreatic adenocarcinoma.

165 citations



Journal ArticleDOI
TL;DR: An immunohistochemical study of c‐erbB‐2 expression was carried out on in situ (non‐invasive) breast carcinoma, using antibody 21N, raised to the intracytoplasmic domain of the c‐ Derbyshire B‐2 oncogene product.
Abstract: An immunohistochemical study of c-erbB-2 expression was carried out on in situ (non-invasive) breast carcinoma, using antibody 21N, raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. Strong membrane staining was observed in 44 out of 74 (59 per cent) cases of ductal carcinoma in situ (DCIS), but none of 48 lobular carcinoma in situ (LCIS) lesions. A detailed comparative morphological evaluation using several different parameters, including histological subtypes, was performed within the DCIS group. The results showed that there was a significant correlation between c-erbB-2 expression and the presence of large cell size, periductal lymphoid cell infiltration, marked nuclear pleomorphism, multinucleation, and a high mitotic rate. Of these, cell size appears to be the most important predictor of c-erbB-2 status, followed by the presence of periductal lymphoid cell infiltration. These results indicate, firstly, that LCIS and DCIS are biologically (as well as histologically) different and, secondly, that a subgroup of DCIS, which is associated with c-erbB-2 over-expression, exists and appears to have distinct histological features. The subgroup of DCIS cases which over-express c-erbB-2 may be a biologically definable category with prognostic importance. These results may therefore have relevance to breast screening programmes, but a larger study incorporating clinical data would be necessary to correlate these findings with clinical outcome.

128 citations


Journal ArticleDOI
TL;DR: The value of PCR in the characterization of genetic defects, prenatal diagnosis, carrier testing, H LA typing, detecting micro‐organisms, identifying activated oncogenes, and in the characterized of leukaemias and lymphomas are discussed.
Abstract: Since publication of the polymerase chain reaction (PCR) technique in 1985 (Saiki et al. Science 1985; 230: 1350-1354), there has been an explosion of reports on its use in medicine and science. We critically review its use both as a diagnostic technique and as a research tool, and show the pathologist how to evaluate PCR data and how to avoid the pitfalls of overinterpretation. We discuss the value of PCR in the characterization of genetic defects, prenatal diagnosis, carrier testing, HLA typing, detecting micro-organisms, identifying activated oncogenes, and in the characterization of leukaemias and lymphomas, and summarize the main applications in biomedical research.

Journal ArticleDOI
TL;DR: The c‐erbB‐2 proto‐oncogene encodes a 190 k Mr protein representing a putative growth factor receptor with considerable homology to the EGF receptor, which is associated with a poor prognosis in breast cancer.
Abstract: The c-erbB-2 proto-oncogene encodes a 190 k Mr protein representing a putative growth factor receptor with considerable homology to the EGF receptor. Gene amplification and overexpression of the oncogene protein have been demonstrated in a variety of tumours including breast cancer, where it is associated with a poor prognosis. In this study we have produced and characterized a mouse monoclonal antibody, designated NCL-CB11, to the c-erbB-2 protein. NCL-CB11 was generated to a synthetic peptide sequence corresponding to a site of predicted antigenicity near the C-terminus of the internal domain of the protein. NCL-CB11 produces intense membrane-associated immunohistochemical staining in a proportion of human cancer cells. The specificity of the antibody is supported by Western blotting and immunoprecipitation studies. Reactivity with an internal site of the protein is confirmed by the necessity of cell permeabilization for reactivity in fluorescence-activated cell sorter (FACS) analysis. A high degree of correlation between immunohistochemical staining using NCL-CB11, and c-erbB-2 gene amplification has been observed. NCL-CB11 should prove to be a valuable reagent for investigations into the pathological significance of c-erbB-2 protein expression.

Journal ArticleDOI
TL;DR: The use of immunohistochemistry for detection of expression of androgen rereptor in prostatic carcinomas may become a new and sensitive method for predicting prostatic tumour behaviour under hormonal therapy and prognosis.
Abstract: Expression of the human androgen receptor was examined in 26 primary prostatic carcinomas by immunohistochemical staining with a polyclonal antibody reactive with the N-terminal domain of the human androgen receptor. Eighteen carcinomas showed homogeneous staining for the androgen receptor, whereas in seven cases a considerable heterogeneity in expression of the receptor was found. In one case, only a very limited number of immunoreactive tumour cells were detected. Comparison of androgen receptor expression with the tumour grading score, according to the MD Anderson grading system, revealed that the proportion of immunostained tumour cells and--to a lesser extent--the intensity of immunostaining were decreased in the more aggressive (grade III) tumours. The use of immunohistochemistry for detection of expression of androgen receptor in prostatic carcinomas may become a new and sensitive method for predicting prostatic tumour behaviour under hormonal therapy and prognosis.

Journal ArticleDOI
TL;DR: It is concluded that the staining time has to be adjusted to the individual silver‐binding characteristics of each tissue block or even each section, and the use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory.
Abstract: This study summarizes our experiences with the silver staining of nucleolus organizer regions (AgNORs) in a total of 580 tumours from ten different tissues. In contrast to other investigators, we made use of automatic image analysis for the evaluation of AgNORs. This provided good reproducibility as determined by the standard cumulative means technique and intra-observer (r1) and inter-observer (r2) agreement in 30 benign (r1 = 0.83-0.95, r2 = 0.76-0.92) and 50 malignant tissue samples (r1 = 0.72-0.85, r2 = 0.51-0.78). By using a series of staining times on sections from 30 tissue blocks taken from the ten types of tissue investigated, considerable variation in the argyrophilic staining of NORs in different tissues and in different blocks from one tumour was shown. The mean AgNOR area of resting lymphocytes or connective tissue cells within tissue blocks of the same organ system varied up to four-fold, even though identical staining times had been used. The most suitable silver reaction time which rendered a good diagnostic difference in the AgNOR content of benign and malignant tissue ranged, for example, in the breast cancer specimens, from 23 to 35 min. We therefore conclude that the staining time has to be adjusted to the individual silver-binding characteristics of each tissue block or even each section. The use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory. This, in turn, is most precisely controlled by morphometry.

Journal ArticleDOI
TL;DR: It is concluded that endothelin‐like immunoreactivity is present in bronchiolar epithelial cells in vivo in rats and mice.
Abstract: We have examined lungs from adult Wistar rats (n = 6) and four different strains of juvenile and adult mice (n = 40) to localize endothelin-like immunoreactivity. Paraffin sections of lung tissue fixed by distension in Bouin's fluid were stained by the peroxidase-antiperoxidase (PAP) method using 10 different rabbit antisera to endothelin. Immunoreactivity was detected in the majority of epithelial cells of conducting airways from the hilum to the periphery and was similar in rats and all four strains of mice studied. Intense immunostaining was detected in mucous, serous and Clara cells and in occasional alveolar pneumocytes type II. Basal cells and most ciliated cells did not immunostain. From these results it is concluded that endothelin-like immunoreactivity is present in bronchiolar epithelial cells in vivo in rats and mice.

Journal ArticleDOI
TL;DR: In all cases, the clinical course was aggressive with rapid and widespread dissemination to internal organs, poor response to conventional chemotherapy, and short survival times, which suggests that although true histiocytic tumours are very rare, their recognition may be important for clinical and/or prognostic reasons.
Abstract: The clinical, histological, immunophenotypic and genotypic properties of four cases of lymphoma of true histiocytic origin are described. The cases were identified by typing 925 non-Hodgkin's lymphomas by immunophenotypic and/or genotypic techniques, and they all presented with skin lesions. The histological and immunophenotypic examination showed dense, diffuse infiltrates of markedly pleomorphic mononuclear cells that were positive for macrophage-associated markers, and negative for B-cell, T-cell and myeloid cell-associated antigens. Staining for Ki-1 and epithelial membrane antigen was also negative. Gene rearrangements studies were performed in three cases, and all of these showed germline configuration of both T-cell receptor and immunoglobulin genes. In all cases, the clinical course was aggressive with rapid and widespread dissemination to internal organs, poor response to conventional chemotherapy, and short survival times (0.5 to 14 months). This suggests that although true histiocytic tumours are very rare, their recognition may be important for clinical and/or prognostic reasons.

Journal ArticleDOI
TL;DR: No rearrangement of bcl‐1, bCl‐2 or c‐myc was found in any case of lymphoma of mucosa associated lymphoid tissue (MALT), providing further evidence that, in spite of having a similar morphology to some other groups of low grade B‐cell lymphoma, lymphomas of MALT comprise a distinct entity.
Abstract: Genotypic analysis has led to the implication of certain oncogenes in the pathogenesis of specific groups of non-Hodgkin's lymphoma. Rearrangements of c-myc are associated with Burkitt's lymphoma and of bcl-2 with centroblastic/centrocytic lymphoma. Rearrangement of bcl-1 has yet to be associated with a specific group of lymphoma. In this study DNA from 62 cases of low grade B-cell lymphoma, classified using the Kiel classification, were analysed by Southern blotting and hybridization with probes to bcl-1, bcl-2, and c-myc. Rearrangements of bcl-2 were found in a proportion of centroblastic/centrocytic lymphoma comparable to other published studies. Rearrangement of c-myc was not found in any case studied. Bcl-1 rearrangement was found in 2/9 cases of B-CLL, and 3/6 cases of centrocytic lymphoma. This incidence of bcl-1 rearrangement in centrocytic lymphoma suggests that it is a characteristic change. No rearrangement of bcl-1, bcl-2 or c-myc was found in any case of lymphoma of mucosa associated lymphoid tissue (MALT), providing further evidence that, in spite of having a similar morphology to some other groups of low grade B-cell lymphoma, lymphomas of MALT comprise a distinct entity.

Journal ArticleDOI
TL;DR: The results indicate that the evaluation of silver‐stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so‐called Jass‐scoring system, and Dukes' classification.
Abstract: Using a one-step silver nitrate staining technique, routinely processed tumour tissues of 49 carcinomas of the colon were investigated to demonstrate silver-stained nucleoli (Ag-nus) and argyrophilic proteins associated with the so-called nucleolar organizer regions (Ag-NORs). Patients with attempted curative resections and tumour stages Dukes' A, B, C1 and C2, with an uneventful follow-up period of at least 48 months (N = 17), showed a statistically significant (P = 0.0001) lower mean number of scattered Ag-NORs (3.04; SD: 1.08) compared to patients who developed metastases during their follow-up period (N = 15; 5.40; SD: 1.28), as well as to patients who underwent palliative surgical treatment (N = 17; 4.48; SD: 1.67). Mean numbers of scattered Ag-NORs per nucleus and staging of the tumour were strongly related (P = 0.0001) to cancer-specific survival. The results indicate that the evaluation of silver-stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so-called Jass-scoring system, and Dukes' classification.

Journal ArticleDOI
TL;DR: An in situ hybridization technique has been developed for the detection of immunoglobulin light chain mRNA in routine pathology specimens using a cocktail of synthetic oligonucleotide probes labelled with biotin or fluorescein 5‐isothiocyanate (FITC) reporter molecules.
Abstract: An in situ hybridization technique has been developed for the detection of immunoglobulin light chain mRNA in routine pathology specimens. The method detects kappa or lambda constant region sequences using a cocktail of synthetic oligonucleotide probes labelled with biotin or fluorescein 5-isothiocyanate (FITC) reporter molecules. The probes were labelled at flanking sites chemically by primary amine directed acylation and by 'homopolymer tailing' with terminal deoxynucleotidyl transferase using non-radioactive nucleotide analogues. The mRNA was unmasked in the formalin-fixed tissue sections by digestion with varying concentrations of proteinase K, and the hybrids were demonstrated using alkaline phosphatase with either a streptavidin/biotin based four-stage system or an anti-FITC antibody based detection system. Alkaline phosphatase was visualized using a Fast Red naphthol-capture method and the sections were counterstained with haematoxylin. The results confirm that the method is specific for kappa or lambda mRNA and show that specific mRNAs can be detected in routine formalin-fixed sections using non-radioactive techniques with retention of good morphology. The method reliably detects light chain mRNA in cells expressing secretory immunoglobulin. The protocol can also be applied to tissue rich in endogenous biotin by using hapten-labelled probes.

Journal ArticleDOI
TL;DR: The results do not support an adverse prognostic effect of c‐erbB‐2 in patients and in a multivariate Cox analysis with other known risk factors the relative risk for cytoplasmic staining alone was 1·456.
Abstract: One hundred and four common epithelial malignancies of the ovary were stained for c-erbB-2 using an affinity-purified polyclonal antibody 21N. Twenty-three out of 104 (22.1 per cent) showed cytoplasmic staining alone. Nine out of 104 (8.7 per cent) showed both membrane and cytoplasmic staining. In a multivariate Cox analysis with other known risk factors the relative risk for cytoplasmic staining alone was 1.456 (chi 2 = 1.71, P greater than 0.1) and for membrane and cytoplasmic staining 0.316 (chi 2 = 7.95, P less than 0.005). These results do not support an adverse prognostic effect of c-erbB-2 in our patients.

Journal ArticleDOI
TL;DR: In various types of glomerulonephritis, immunofluorescent staining for type I collagen was positive in the fibrocellular and fibrous crescents, sclerosed glomeruli, and infrequently within the glomerular mesangium, but was less in amount and frequency compared with type III collagen staining.
Abstract: The distribution of type I collagen in normal and diseased renal tissues was studied using immunofluorescence and immunoelectron microscopy, and was compared with that of type III collagen. In normal human kidneys, a monoclonal antibody against type I or type III collagen reacted with the renal interstitium, but not with the intra-glomerular structures. In various types of glomerulonephritis, immunofluorescent staining for type I collagen was positive in the fibrocellular and fibrous crescents, sclerosed glomeruli, and infrequently within the glomerular mesangium. In the crescents and sclerosed glomeruli, type I collagen was co-localized with type III collagen. The staining intensity of type I collagen in those areas was generally stronger than that in the interstitium. Mesangial staining for type I collagen was present within the glomeruli, particularly with a marked mesangial matrix increase, but was less in amount and frequency compared with type III collagen staining. These findings indicate that the fibrosclerotic process in damaged glomeruli is accompanied by the appearance of interstitial collagens, and that participation of type I collagen is prominent in crescent organization and global glomerular sclerosis, but is less frequent in mesangial expansion, compared with type III collagen.

Journal ArticleDOI
TL;DR: The distribution of cells expressing the integrins VLA‐1 to 6 in human intestine was examined by alkaline phosphatase immunohistochemistry using monoclonal antibodies specific for the individual α‐chains of the VLA heterodimer.
Abstract: The distribution of cells expressing the integrins VLA-1 to 6 in human intestine was examined by alkaline phosphatase immunohistochemistry using monoclonal antibodies specific for the individual alpha-chains of the VLA heterodimer. VLA-2,3, and 6 were expressed on all epithelial cells in the small and large bowel. VLA-1 was expressed on crypt cells in the small and large bowel, but was only weakly expressed or was absent on villus epithelial cells in the small bowel and colonic surface epithelial cells. All epithelia were negative for VLA-4 and VLA-5. Intraepithelial lymphocytes were VLA-1+ and VLA-4+. VLA-1,3, and 5 were expressed uniformly by muscularis propria, muscularis mucosae, pericrypt cells, and smooth muscle fibres within the villi. By contrast, VLA-2 and 4 were present only in pericrypt cells and fibres within the villi; they were absent from the muscularis mucosae. VLA-1,3,5, and 6 were expressed by endothelium. Staining of muscle fibres and endothelium in the lamina propria made it difficult to determine the extent of VLA expression on lamina propria lymphocytes. However, VLA-1+ cells with lymphoid morphology were only rarely seen. All mononuclear cells in the lamina propria were VLA-4+.

Journal ArticleDOI
TL;DR: High Ki‐67 and S‐phase levels correlated with advanced disease stage and patient survival but not with OR or PR status, suggesting that hormone‐receptor pathways and proliferative activity are not related in ovarian cancer.
Abstract: Steroid hormone receptors and reactivity for Ki-67 proliferation antigen were studied immunohistochemically in non-neoplastic post-menopausal human ovary and in 29 ovarian cancers. In the normal ovary, oestrogen (OR) and progesterone receptors (PR) were found in the surface epithelium and PR also in the ovarian stroma. Of the ovarian carcinomas 38 per cent (11/29) contained OR and 69 per cent (20/29) PR. Oestrogen receptor expression was confined to malignant cells, whereas PR was present occasionally also in the tumour stroma. In most cases, ORs and PRs were found only in a small population of cancer cells. The growth fractions assessed by the percentage of Ki-67-positive cells ranged from 1 to 59 per cent (mean 19.7 per cent) with a significant correlation (r = 0.74, P less than 0.0001) to S-phase values (mean 12.9 per cent, range 1.2-25.9 per cent) determined by DNA flow cytometry. High Ki-67 (greater than or equal to 15 per cent) and S-phase levels (greater than or equal to 7.5 per cent) correlated with advanced disease stage and patient survival but not with OR or PR status, suggesting that hormone-receptor pathways and proliferative activity are not related in ovarian cancer. Positive OR status, however, identified patients with a better prognosis (P = 0.02), suggesting a correlation with tumour differentiation. The independent prognostic value of oestrogen receptor status and Ki-67 remains to be determined, but the prognostic impact of Ki-67 was comparable to that of S-phase values.

Journal ArticleDOI
TL;DR: The lungs from 16 cases of plexogenic pulmonary arteriopathy obtained at heart‐lung transplantation were examined by electron microscopy and suggested that occlusion of small pulmonary arterial vessels by myofibroblasts may be at least as important as vasoconstriction in the early elevation of the pulmonary vascular resistance in primary pulmonary hypertension.
Abstract: The lungs from 16 cases of plexogenic pulmonary arteriopathy obtained at heart-lung transplantation, half of which had primary pulmonary hypertension, were examined by electron microscopy. From these the probable pathogenesis of pulmonary arterial intimal fibrosis in plexogenic pulmonary arteriopathy was deduced. The earliest detectable change was migration of smooth muscle cells from the media, through the internal elastic lamina into the intima. These cells collected beneath the endothelium and lost many of their myofilaments to become myofibroblasts. They were associated with ground substance but scanty collagen fibrils. As the quantity of interstitial collagen increased, the myofibroblasts reverted to a muscular structure, became elongated, and assumed a regular, circumferential orientation. This later stage coincided with the development of plexiform lesions. At both early and later stages, the muscular pulmonary arteries were contracted but not markedly so, and muscular evaginations were not seen. On the other hand, the cellular intimal proliferations developed early and were occlusive. This suggests that occlusion of small pulmonary arterial vessels by myofibroblasts may be at least as important as vasoconstriction in the early elevation of the pulmonary vascular resistance in primary pulmonary hypertension.

Journal ArticleDOI
TL;DR: The application of microwave irradiation is extended to include the acceleration of the streptavidin‐biotin peroxidase staining procedure for the detection of a wide range of antigens in paraffin‐embedded sections of both normal and neoplastic tissues.
Abstract: The application of microwave irradiation is extended to include the acceleration of the streptavidin-biotin peroxidase staining procedure for the detection of a wide range of antigens in paraffin-embedded sections of both normal and neoplastic tissues. Microwave irradiation is used for all procedural steps requiring incubation so that the entire staining procedure can be completed within 20 min. The technique is simple and convenient, with uniform irradiation times for different tissue antigens. The results obtained equalled that of conventional staining procedures.

Journal ArticleDOI
TL;DR: In non‐neoplastic trophoblastic tissue AgNOR counts are clearly a reflection of ploidy rather than of cell proliferation, and should not be confused with those in hydropic abortions or complete moles.
Abstract: There is considerable debate as to whether AgNOR counts reflect cellular ploidy or cellular proliferation. Trophoblastic tissue from hydropic abortions and from hydatidiform moles offers an excellent model for analysing this problem. Thus, complete moles show considerable cell proliferation but are diploid, whilst partial moles show markedly less cell proliferation but are triploid: hydropic abortuses are diploid and show no cellular proliferation. AgNOR counts in villous cytotrophoblastic cells from hydropic abortions and from complete hydatidiform moles are similar, but those in partial hydatidiform moles are 50 per cent higher than in either hydropic abortions or complete moles. Thus, in non-neoplastic trophoblastic tissue AgNOR counts are clearly a reflection of ploidy rather than of cell proliferation.

Journal ArticleDOI
TL;DR: This study demonstrates the expression of endothelin in a number of pulmonary tumours and suggests a possible role for this peptide in the growth and/or differentiation of these tumours.
Abstract: Paraffin sections of 66 surgically resected lung tumours were immunostained with antisera to human endothelin-1 and to the C-terminal peptide of big endothelin. With both antisera, strong immunoreactivity was demonstrated in 11 of 15 squamous cell carcinomas and 11 of 16 adenocarcinomas. Focal immunoreactivity was seen in small cell carcinoma (2/12), large cell carcinoma (2/5), and carcinoid tumours (2/11). Four lymphomas and three sarcomas did not show endothelin immunoreactivity. Cryostat sections of 22 of the 66 tumours were hybridized with radiolabelled complementary RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization demonstrated the presence of endothelin mRNAs in 4 of 7 squamous cell carcinomas and in 5 of 8 adenocarcinomas, in a pattern similar to that shown by immunocytochemistry. No hybridization signals were obtained from the other types of tumours. In lung tissue adjacent to the tumours, endothelin-like immunoreactivity and mRNA were detected in pulmonary endocrine cells and, in some cases, other epithelial cells, and in alveolar capillary endothelial cells. This study demonstrates the expression of endothelin in a number of pulmonary tumours and suggests a possible role for this peptide in the growth and/or differentiation of these tumours.

Journal ArticleDOI
TL;DR: It is found that immunostaining with QBEnd/10 aids the diagnosis of Kaposi's sarcomas and allows their distinction from other spindle cell neoplasms of skin in routinely processed material.
Abstract: Kaposi's sarcomas are seen more commonly in routine histopathology laboratories since the advent of the more widespread and aggressive variant of the disease associated with HIV infection Distinguishing nodular lesions from other spindle cell and vascular tumours can sometimes be difficult Immunohistochemistry has been disappointing as a diagnostic aid, often requiring special fixation or frozen tissue and even then, staining of spindle cells has been variable We describe the use of the new IgG1 mouse monoclonal antibody raised against human placental endothelial cells, QBEnd/10, on routine formalin-fixed, paraffin-embedded tissue A retrospective study was performed on 22 Kaposi's sarcomas of skin including patch, plaque, and nodular lesions and compared with 38 other vascular and spindle cell tumours from skin All sections were stained with haematoxylin and eosin, QBEnd/10, Ulex europaeus agglutinin 1 (UEA-1) and for factor VIII-related antigen (FVIIIRAg) The results demonstrate that spindle cells in lesions from Kaposi's sarcomas, but not other vascular or spindle cell tumours, immunostain clearly with QBEnd/10 Immunostaining for FVIIIRAg shows only weak and irregular positivity of the spindle cells, whilst staining with UEA-1 is consistently negative We find that immunostaining with QBEnd/10 aids the diagnosis of Kaposi's sarcomas and allows their distinction from other spindle cell neoplasms of skin in routinely processed material

Journal ArticleDOI
TL;DR: It is found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP and PTHp peptides and no staining with anti‐PTHp antiserum could be detected immunohistochemically in any of the parathyroids.
Abstract: Parathyroid hormone-related protein (PTHrP) is invoked as the cause of humoral hypercalcaemia of malignancy (HHM); it is contained in the keratinocyte layer of normal skin; and there is evidence that is is produced by fetal parathyroids. Antibodies against synthetic PTHrP peptides have been raised in rabbits and sheep. This immunohisto-chemical study has found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP(1–34) and PTHrP(50–69). Primary hyperplastic glands are negative. No staining with anti-PTHrP(106–141) antiserum could be detected immunohistochemically in any of the parathyroid adenomata or hyperplasia.

Journal ArticleDOI
TL;DR: S100 immunoreactivity is not a reliable means of differentiating between luminal epithelial and myoepithelial cells, and the possibility that staining with antibody to S100 protein may be affected by methods of fixation and immunohistochemical technique is discussed.
Abstract: The expression of S100 protein, as assessed by immunohistochemistry, has been evaluated in 101 mammary carcinomas of various histological types, including Paget's disease of the nipple. S100 immunoreactivity was seen in 44 of 101 primary carcinomas, including in situ lesions. It was present in all histological types, with the exception of mucoid carcinoma. In the 33 cases with associated Paget's disease of the nipple, S100 expression was seen in the Paget's cells in six cases. S100 immunoreactivity has been suggested as a marker of myoepithelial cells, but in our hands staining of these cells is less consistent using the S100 antibody than with antibodies to actin. Furthermore, S100 protein is also expressed by some luminal epithelial cells. Therefore, in contrast to actin immunoreactivity, S100 immunoreactivity is not a reliable means of differentiating between luminal epithelial and myoepithelial cells. The possibility that staining with antibody to S100 protein may be affected by methods of fixation and immunohistochemical technique is discussed.