Papillomaviruses, p53, and cervical cancer.
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Genes, p53↗
Biomedical subjects
D A Levison
Publications and source records attributed to D A Levison.
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↗
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↗
Identification of titanium in human tissues.
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Histocytochemistry↗
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↗
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↗
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↗
Identification of titanium pigment in drug addicts' tissues.
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Adult↗
Sclerosing lymphocytic lobulitis of the breast--evidence for an autoimmune pathogenesis.
We describe 13 cases of inflammatory lesion of breast lobules in young and middle-aged women, presenting as breast lumps, with, in five cases, associated breast pain. The patient with the most florid bilateral disease subsequently developed Hashimoto's thyroiditis. This prompted us to consider an autoimmune pathogenesis for all the breast lesions. We confirm a previously documented association of such breast lesions with diabetes mellitus and review the evidence for a possible HLA association. Increased HLA-DR expression by breast epithelial cells was observed in cases available for study. Of the seven patients screened for circulating autoantibodies, three had none, one had smooth muscle antibodies, one parietal cell, one parietal cell and thyroid microsomal, and the seventh had the thyroid autoantibodies expected in Hashimoto's disease. Five of seven patients whose HLA-status was determined were HLA-DR3, 4 or 5 positive, either singly or in combination. Immunophenotypic analysis of the mammary lymphoid infiltrate showed that the majority of infiltrating lymphocytes were B-cells.
Autoantibodies↗
The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S+G2+M phase fraction (flow cytometric analysis) and prognosis.
PCNA is a nuclear protein that is synthesized in late G1 and S phases of the cell cycle and is, therefore, correlated with the cell proliferative state. A new monoclonal antibody (PC10) to genetically engineered PCNA has been shown to label proliferating cells in formalin-fixed paraffin-embedded normal human tissues. Previous studies in lymphomas, using various markers of cell proliferation, have shown a strong correlation between indices of cell proliferation and histological grade. These studies have shown that within each histological subtype there is often a wide range of proliferative indices and that these may be of some prognostic significance. Thirty-one gastrointestinal lymphomas were studied. Our results show that there is a good correlation between PC10 index and histological grade of tumour (0.01 P greater than P greater than 0.001) and also a significant relationship between PC10 index and S+G2+M phase fraction as measured by flow cytometric analysis (r2 = 0.62; P less than 0.01). Twenty-three cases were available for survival analysis. In these cases a high PC10 score correlated with poor survival (P = 0.04). Based on this series, it appears that there is a significant relationship between PC10 index and histological grade, and between PC10 index and S+G2+M phase as measured by flow cytometric analysis. In addition, our results suggest that a high PC10 index is an adverse prognostic factor in primary gastrointestinal lymphoma.
Cell Cycle↗
Haemangiopericytomas: the prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA).
Forty-two cases of haemangiopericytoma were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to PCNA. The percentage of tumour cells with positive staining for PCNA was found to correlate well with histological grading. Clinical follow-up data were available in 25 adults and showed no known deaths in 11 cases with a low proportion (less than 14%) of positive cells. Out of 14 cases with a high number (greater than or equal to 14%) of positive cells, seven patients are known to have died, two had metastases, and in a further two there have been multiple recurrences of tumour. DNA flow cytometry was performed on 26 cases but this showed no correlation with PC10 staining or clinical outcome. Staining with PC10 may be of particular value in the identification of patients at greatest risk of rapid tumour metastasis and early death.
Adolescent↗
Calcium pyrophosphate dihydrate deposition disease: morphological and microanalytical features.
The light microscopic and polarization appearances of calcium pyrophosphate dihydrate crystal deposits in tissues are reviewed. In routine sections haematoxylinophilic crystalline deposits with a feathery or brush-like pattern are typical of calcium pyrophosphate dihydrate. Short rhomboidal crystals showing positive birefringence are seen on polarization; X-ray microanalytical and infrared spectroscopic data support the specificity of these appearances. The appearances of the crystal deposits in decalcified specimens are also described. We include six cases of calcium pyrophosphate dihydrate deposition within periarticular bone; to the best of our knowledge this has not previously been described.
Aged↗
Prognostic value of proliferating cell nuclear antigen in gastric carcinoma.
A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising.
Adult↗
Malignant lymphoma in the gastrointestinal tract.
The main function of gut-associated lymphoid tissue is to provide an adaptive protective mechanism to help defend the body from exogenous antigen. This complex function requires the coordination of various cellular elements, including B cells, T cells, macrophages, and the epithelial cells of the gut. The control of this remains poorly defined, but involves various cellular subpopulations, humoral factors acting by autocrine and paracrine means, and cell adhesion molecules regulating tissue tropisms. Disruption of these cybernetic mechanisms is likely to be fundamental to the development and behavior of gut lymphomas. Although conventional histopathology is likely to remain the mainstay of diagnosis and patient management, further advances in the understanding, diagnosis, and therapy of gut lymphomas will require a greater knowledge of the cells and molecules that regulate the lymphoid milieu of the gut.
Gastrointestinal Neoplasms↗
Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms.
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.
Adult↗
The gut-associated lymphoid tissue and its tumours.
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Gastrointestinal Neoplasms↗
Jejunal water and sodium secretion occurs in chronic idiopathic intestinal pseudo-obstruction.
We observed jejunal water and sodium secretion in two patients with chronic idiopathic intestinal pseudo-obstruction by standard perfusion techniques. The ability of glucose to reverse this secretory state was impaired. These observations suggest that a jejunal secretory state may contribute to the diarrhea in chronic idiopathic intestinal pseudo-obstruction.
Adult↗
Weddellite calcification in the breast: eighteen cases with implications for breast cancer screening.
Breast tissue obtained from 18 of 246 women (7.3%) having localization biopsy for microcalcification contained crystals of Weddellite (calcium oxalate dihydrate). This was characterized by microscopic infra-red spectroscopy in three cases. Weddellite calcification was associated with benign lesions in 16 cases, but incidental atypical lobular hyperplasia and lobular carcinoma in situ were present, each in one case. Pathologists should be aware of this common non-haematoxyphilic, birefringent form of breast micro-calcification. Its presence has implications for the examination of biopsy specimens resulting from breast cancer screening using mammography.
Adult↗