Biomedical subjects
Publications and source records attributed to P H Maddox.
Data on the quality of a modified method for producing multiblocks from conventional blocks of paraffin wax embedded histological material are reported. Originally devised as a way of assessing antibodies for immunohistology, the technique is particularly suited to producing a set of reference and teaching material for use by trainee and senior pathologists.
AIMS: To determine the best of five antibodies for immunohistochemical assessment of growth fraction in formalin fixed, paraffin wax embedded tissues. METHODS: Sections from 100 recent, and 17 ten year old or over wax embedded blocks of normal and malignant tissues were immunostained with monoclonal Ki67, polyclonal Ki67, PC10, MIB1, and JC1. The antibodies were evaluated for specificity of nuclear versus cytoplasmic staining, cleanliness of background, and compared with the expected pattern of staining in normal tissues, defined immunohistochemically by monoclonal Ki67 antibody in frozen tissues or by tritiated thymidine uptake. RESULTS: No marker was ideal, but best results were obtained with MIB1 and polyclonal Ki67, followed by JC1, PC10, and monoclonal Ki67. CONCLUSIONS: For routine use, MIB1 or polyclonal Ki67 are the best proliferation markers in conventional histological preparations. The other markers tested cannot be recommended.
Langerhans cells (LCs) are dendritic, antigen-presenting cells found in the epidermis. This study investigates the effect of early breast cancer on the expression of CD1a and S100 antigens by these cells. LCs were counted and expressed as cells/mm of epithelial basement membrane on biopsies from the skin overlying the tumour and from biopsies distant from the tumour. A control study was performed on normal breast skin, not adjacent to a lesion, from women with benign breast disease. The LC count of 18 patients undergoing biopsy for benign breast disease indicated a mean of 26 cells/mm [95 per cent confidence interval (CI) 23-29] and a S100/CD1a ratio of 70 per cent. In 35 cases of early breast cancer, the CD1a-positive LC count in the epidermis overlying the carcinoma (mean 26/mm; 95 per cent CI 23-29) was similar, but the count made on biopsies distant from the tumour (mean 21/mm; 95 per cent CI 19-23) was significantly smaller. The percentage ratio of S100/CD1a was 71 per cent over the carcinoma and 84 per cent in the distant biopsies. The changes were not associated with the presence of nodal metastases or the oestrogen and progesterone status of the primary tumour. The reduction in LC numbers provides a link between decreased monocyte function and the decreased skin hypersensitivity responses found in patients with breast cancer.
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Previous work in our department demonstrated a reduction in the numbers of Langerhans' cells in cervical epithelium showing histologic changes of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). In conjunction with a localized reversal of the T4:T8 ratio of T-lymphocytes, that finding provides evidence of the association of epithelial immunosuppression with both HPV infection and CIN. To investigate whether that phenomenon occurs primarily because of HPV alone or might be caused by a cofactor (e.g., cigarette smoking, oral contraceptive use, chlamydial infection), we performed a study of the effect of those cofactors on the immune defenses of the cervical epithelium. In a study of Langerhans' cells we showed that infection with HPV type 16 and current cigarette smoking both exert effects that cause a reduction in those cells. That diminution of the major antigen-presenting cells in cervical epithelium may constitute a mechanism that explains the observed role of those agents in the etiology of cervical neoplasia.
Langerhans' cells in cervical epithelium in colposcopic biopsy specimens were identified by immunocytochemical staining for S100 protein and T6 (CD1) antigen, and their density was quantified. Possible cofactors for the development of cervical neoplasia were examined for any effect on the cell counts per unit area. Current cigarette smoking was associated with a significant decrease in the Langerhans' cell population in both normal epithelium and lesions due to cervical intraepithelial neoplasia. Ex-smokers tended to have cell counts between those of smokers and non-smokers. There was a dose-response relation between number of cigarettes smoked daily and effect on cell counts. These findings of a local immunological effect of smoking on cervical epithelium may explain the means by which cigarette smoking contributes to the development of cervical neoplasia.
A formalin-calcium fixation method of preparing cryosections is described, which allows demonstration of Langerhans' cells by S100 antigen staining on frozen sections. The number of Langerhans' cells given by T6 antigen staining is also higher in formalin-calcium fixed frozen sections than acetone fixed frozen sections. The preparation is suitable for dual demonstration of the two antigens on the same section enabling a more accurate numerical evaluation of Langerhans' cell populations in the normal cervical epithelium.
Immunocytochemical staining for papillomavirus antigen was carried out on 1147 consecutive cervical punch biopsy specimens over 12 months. Of 876 cases with cervical intraepithelial neoplasia (CIN) 351, were antigen positive and of 49 cases with histological evidence of human papillomavirus (HPV) infection but no CIN, 14 were positive. There were 204 cases reported to be normal on routine histological examination and 12 cases reported to show features suggestive but not diagnostic of HPV infection. Of the normal group, 24 (12%) were antigen positive and of the equivocal group, two were positive. In 122 of the normal or equivocal groups cytological examination was repeated at the time of colposcopy, and dyskaryosis was reported in 36. In only four cases was disease shown by HPV antigen staining when there was no diagnostic histological or cytological abnormality. HPV antigen staining assists in the recognition of the range of histological changes associated with productive HPV infection but is an insensitive test and has only limited value in supplementing histological and cytological examinations as a diagnostic aid in routine colposcopic pathology.
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