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Biomedical subjects

D A Levison

Publications and source records attributed to D A Levison.

At least 37 records · Page 2Linked to original sources
PubMed1993

TGF alpha and TGF beta expression in mammary carcinoma.

TGF alpha and beta expression was examined using rabbit polyclonal antibodies and immunohistochemistry on a series of 195 breast carcinomas. TGF alpha immunoreactivity was observed in all but nine of the tumours, with over 50 per cent staining strongly. The polyclonal TGF alpha antibody (CIM1), when compared with a commercially available mouse monoclonal TGF alpha antibody used on the same sections, gave a good correlation (r = 0.52, P < 0.001). Both TGF alpha antibodies produced a granular cytoplasmic staining pattern, that with CIM1 being coarser, suggestive of binding to an aggregated protein or organelle. Eighty-one per cent of tumours stained with the TGF beta antibody, 35 per cent strongly. There was significant co-expression of TGF alpha and TGF beta (P < 0.001). However, they were not found to be useful prognostic indicators, lacking any significant correlation with histological classification, tumour size, nodal status, oestrogen receptor status, S-phase fraction, or overall survival over a 9-12 year period. The expression of these growth factors in most breast carcinomas suggests that they have important biological roles, but the exact nature of these roles remains unclear at the moment.

Adult↗
PubMed1993

Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis?

In an immunohistochemical pilot study of 195 primary breast cancer patients with a 10-year median follow-up we found that patients with carcinomas who express p53 protein in the majority of their tumor cells (19% of the cases) have a considerably worse prognosis than those who do not. The effect of the presence of the protein is seen on disease-free interval (chi-square, 11.69; P < .001), overall survival (chi-square, 19.68; P < .001), and survival after relapse (chi-square, 4.93; P < .02), and is seen in node-negative (chi-square, 6.99; P < .009) and node-positive (chi-square, 13.05; P < .001) patients. Furthermore, the effect is most apparent in patients with infiltrating lobular and grade II infiltrating ductal carcinomas (chi-square, 27.97; P < .001) that have a rather heterogeneous clinical behaviour and are difficult to subdivide on the basis of currently available markers. Cox multivariate analysis shows that p53 majority staining is second only to node status in significance of effect on overall survival.

Adult↗
PubMed1993

Posttransplant cutaneous lymphoma.

BACKGROUND: Posttransplant lymphoma is closely associated with Epstein-Barr virus (EBV) infection and appears to have a predilection for extranodal sites. We describe four cases of primary cutaneous posttransplant lymphoma. OBJECTIVE: Our aim was to determine cell lineage and any possible association with EBV in each case of cutaneous lymphoma. METHODS: Tumor tissue was examined by light microscopy, immunohistochemistry, nonisotopic in situ hybridization and polymerase chain reaction. RESULTS: The data were consistent with a diagnosis of EBV-associated cutaneous B-cell lymphoma in three cases and cutaneous T-cell lymphoma not associated with EBV in one case. No patient with B-cell lymphoma had extracutaneous involvement during a mean follow-up of 3.9 years. The patient with cutaneous T-cell lymphoma died of cerebral involvement 9 months after initial presentation. CONCLUSION: These data suggest a possible role for EBV infection in the origin of cutaneous B-cell lymphoma in immunosuppressed patients.

Aged↗
PubMed1993

Amyloid arthritis associated with IgM kappa lymphoplasmacytoid lymphoma.

Amyloid arthritis is an uncommon cause of locomotor disease and may closely resemble RA. Macroglobulinaemia is rarely associated with amyloidosis and there has been only one report of amyloid arthritis in this setting, the patient having had Waldenstrom's macroglobulinaemia. We report the occurrence of amyloid joint disease in the course of an IgM kappa B-cell dyscrasia which evolved over 16 years to an overt lymphoplasmacytoid lymphoma.

Amyloidosis↗
PubMed1993

p53 immunoreactivity in human malignant melanoma and dysplastic naevi.

Expression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM-1, an antiserum raised against recombinant human p53 protein. Because wild-type p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post-translational mechanisms or gene mutation. A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P < 0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P = 0.008). These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.

Dysplastic Nevus Syndrome↗
PubMed1993

Gold in the dermis following chrysotherapy: histopathology and microanalysis.

Paraffin-embedded sections of skin from patients with rheumatoid arthritis treated with gold who had developed skin rashes were examined by light microscopy and scanning electronmicroscopy with microanalysis. Sparse, small, brown or black granules in plump, often elongated cells in the dermis were shown to contain gold by energy dispersive X-ray microanalysis. These cells expressed some macrophage markers. The amount of gold present showed some correlation with the total gold dose. Gold was not confined to lesional skin. In one case where uninvolved skin was examined, more gold was found there than in lesional skin.

Aged↗
PubMed1993

Patterns of immunohistochemical staining for proliferating cell nuclear antigen and p53 in benign and neoplastic human endometrium.

Immunohistochemical staining was carried out on a spectrum of normal, hyperplastic and malignant endometrial curettings, for proliferating cell nuclear antigen--PCNA (using the monoclonal antibody PC10) and for abnormally stabilized p53 (using the polyclonal antibody CM-1). The mean proportion of glandular epithelial cells showing PCNA immunoreactivity was significantly lower in atypical hyperplasia/intra-endometrial adenocarcinoma than in invasive adenocarcinoma, but the degree of overlap between the cases was such that this was not considered to be of diagnostic value. p53 immunoreactivity was detected in 47% of invasive adenocarcinomas and in a much smaller proportion of endometria showing simple hyperplasia and atypical hyperplasia, but staining was only focal in the last two conditions. The majority of p53-positive invasive adenocarcinomas had a large proportion of glandular epithelial cells expressing PCNA, but a significant number of p53-negative cases also had a high PC10 index. This suggests that, in endometrial neoplasia, there is not a simple relationship between abnormally stabilized p53 and PCNA expression.

Adenocarcinoma↗
PubMed1993

Proliferating cell nuclear antigen (PCNA) and nucleolar organiser regions in Hodgkin's disease: correlation with morphology.

AIM: To define the distribution of proliferating cell nuclear antigen (PCNA) and silver staining nucleolar organiser regions (AgNORs) in Hodgkin's disease. METHODS: PCNA was shown in a series of 34 cases of Hodgkin's disease using immunohistochemical methods. In a second series of 46 cases the AgNOR technique for interphase nucleolar organiser regions was studied. Both series comprised routinely fixed and processed paraffin wax sections of three main Rye subtypes. RESULTS: In all cases, regardless of Rye subtype, most Sternberg-Reed cells and mononuclear Hodgkin cells showed nuclear PCNA immunoreactivity and such cells had 15 or more AgNOR sites. The Hodgkin cells had, in general, about half the number of AgNORs seen in Sternberg-Reed variants. CONCLUSIONS: These data support the notion that Hodgkin's disease can be regarded as a high grade lymphoma, the large Hodgkin's and Sternberg-Reed cells being the (PCNA positive and AgNOR rich) neoplastic elements with high proliferative capacity. A smaller proportion of the associated cells also showed evidence of proliferation.

Antigens, Neoplasm↗
PubMed1992

A comparison of proliferating cell nuclear antigen (PCNA) immunostaining, nucleolar organizer region (AgNOR) staining, and histological grading in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours are lesions in which it is difficult to predict clinical outcome from the histological appearances. Sixty cases were studied using three different methods of assessing aspects of cellular proliferation; these were (i) immunostaining for proliferating cell nuclear antigen (PCNA), (ii) interphase nucleolar organizer region staining (AgNORs), and (iii) a histological grading system based on mitotic counts. Both PCNA immunostaining and AgNOR counts were found to correlate well with histological grading and all three methods independently showed good correlations with survival. This suggests that these proliferation-associated markers may be used as additional features to support histological grading in this relatively uncommon group of tumours.

Antigens, Neoplasm↗
PubMed1992

The assessment of cellular proliferation by immunohistochemistry: a review of currently available methods and their applications.

Immunohistochemical methods using antibodies to cell cycle-related antigens may be used as a means of assessing various aspects of proliferation in tissue, and have the important advantage of preserving the spatial orientation of proliferating cells in histological sections. Currently, the most widely available antibodies for this purpose are antibodies to bromodeoxyuridine (BrdU), Ki67 and antibodies to proliferating cell nuclear antigen (PCNA). BrdU is a thymidine analogue incorporated during the S phase of the cell cycle, which can be introduced by 'in vitro' incubation, and monoclonal antibodies are available to display its localization. Ki67 demonstrates a nuclear antigen expressed in all phases of the cell cycle, except G0 and early G1, but can only be applied to frozen tissue. PCNA is a nuclear antigen which is essential for DNA synthesis, two commercially available antibodies to PCNA work in paraffin-embedded tissue, but may have different staining characteristics under different conditions of fixation. The main advantages and disadvantages of these different techniques are discussed, together with their main applications to date.

Antibodies, Monoclonal↗
PubMed1992

An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.

Biopsy↗
PubMed1992

Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer.

Expression of the cellular p53 tumour-suppressor protein was examined in 78 epidermal tumours, including basal and squamous cell carcinomas, keratoacanthomas, solar keratoses, Bowen's disease and viral warts. An immunohistochemical study was employed using the antibody CM-1, raised against recombinant human p53 protein. Positive staining for p53, not detectable in normal cells because wild-type p53 is rapidly degraded, reflects abnormal stabilization of p53 protein, and in many cases suggests p53 gene mutation. p53 immunoreactivity was not observed in normal skin or in viral warts. In contrast, positive staining for CM-1 was seen throughout the tumour in the majority of basal and squamous cell carcinomas and in Bowen's disease. Immunoreactivity to p53 was also observed in the majority of keratoacanthomas and solar keratoses, but was confirmed to areas of dysplastic basal epithelium. This study demonstrates that accumulation of p53 protein, suggestive in many cases of p53 gene mutation and hence loss of tumour-suppressor function, may occur as an important early step in the development of diverse epidermal cancers.

Bowen's Disease↗
PubMed1992

Histopathological and microanalytical study of zirconium dioxide and barium sulphate in bone cement.

AIMS: To report the appearances of zirconium dioxide and barium sulphate in interface membranes, synovium, and other tissues around joint prostheses. METHODS: Histological sections from 23 specimens were reviewed by light microscopy and polarisation. Scanning electron microscopy and x ray microanalysis were performed on routinely processed paraffin wax sections. RESULTS: Polyethylene, metals, and polymethylmethacrylate cement debris were easily recognisable. Almost all the cement remnants contained either zirconium dioxide or barium sulphate, confirmed by microanalysis. The contrast media had characteristic light microscopic appearances. Zirconium was identified in macrophages away from cement remnants. CONCLUSION: The presence of radiographic contrast media in tissues around prosthetic joints is common but not widely recognised.

Adult↗