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Biomedical subjects

P N Cowen

Publications and source records attributed to P N Cowen.

At least 19 recordsLinked to original sources

Classical oestrogen receptor is not detectable in pancreatic adenocarcinoma.

Recent reports have suggested the presence of oestrogen receptors (ER) in pancreatic carcinoma. Therefore the tumour may be sensitive to hormone manipulation therapy. We examined 23 biopsies of human pancreatic carcinoma tissue for the presence of ER. The tissue was assayed by two methods: Iso-electric focusing (IEF) and ER-ICA an immunocytochemical assay. All biopsies were tested with ER-ICA and ten by IEF. Each biopsy was assessed histologically for tumour content and 20 contained adenocarcinoma. None of the samples of pancreatic carcinoma were positive for ER using the ER-ICA, and none demonstrated the binding peak typical of ER in the IEF assay. These results suggest that in pancreatic carcinoma oestrogen receptor is either absent (or at very low levels), or of a different type to that found in breast and uterine tissue. On theoretical grounds at least, this must raise questions as to the oestrogen sensitivity of pancreatic cancer.

Adenocarcinoma↗

Mucous metaplasia of the pleura.

A case of mucous metaplasia of mesothelium in an 80 year old woman is described. Its cause is unknown, but it is important not to confuse it with secondary tumour.

Aged↗

Oestrogen receptor in breast cancer: prognostic studies using a new immunohistochemical assay.

A recently developed and validated histochemical method--immunogold-streptavidin enhancement--was used to determine oestrogen receptor content in paraffin sections of breast cancers. The selection of the best cut-off point to define oestrogen receptor status as rich or poor was made on the basis of survival data, using the following indices: survival to term; disease-free interval; survival at 5 years; and disease-free interval at 5 years. Oestrogen receptor status was examined in relation to histological grade, lymph node status, menopausal status and tumour size and these four indices were considered as independent prognostic factors. Semi-quantitative assay of receptor content showed that increasing content was related to better prognosis. Adjuvant therapy alone had no effect on patient outcome. Independently, histological grade and lymph node status, but not menopausal status or tumour size, were prognostic indicators. Oestrogen receptor rich status, as measured by immunogold-streptavidin, in conjunction with certain of these factors indicated a better prognosis. This was comparable with results in reports using other methods of receptor assay. We found the oestrogen receptor status and menopausal status more significant at 5 years than at term. The advantage of immunogold-streptavidin enhancement, which we found as reliable as other methods for oestrogen receptor assay, is that it can be used on archival, routinely paraffin-processed material.

Breast Neoplasms↗

Development and validation of a sensitive immunohistochemical oestrogen receptor assay for use on archival breast cancer tissue.

In a preliminary paper (Teasdale et al. 1987) comparing the oestrogen receptor (ER) content of breast cancers by the biochemical dextran coated charcoal (DCC) method and by two histochemical methods, peroxidase immunocytochemistry (ERICA) and immunogold-silver staining (IGSS), it was indicated that ERICA is more sensitive than DCC and that IGSS is as specific as ERICA but less sensitive. This paper describes the comparison of the above three assay methods with two other biochemical methods, iso-electric focusing (IEF) and an enzyme immuno-assay (EIA) on a larger number of cancers. All methods gave statistically comparable results except that IGSS remained less sensitive than the rest. Various modifications to IGSS showed that an immunogold streptavidin enhancement method (IG-SAM) produced sensitivity and specificity equal to that of ERICA. Since IGSS and its modifications are the only methods which can be used on archival paraffin-embedded cancers and IG-SAM gives results highly comparable to ERICA, retrospective studies can be performed on patients whose outcome and response to various treatments are known. Most recent studies have shown that ER positive results can be obtained from 10-year-old paraffin blocks.

Antibodies, Monoclonal↗

Late Niemann-Pick disease with neurovisceral storage: a classification problem.

A 51 year old man presented in 1969 with slowly progressive cerebellar ataxia of unknown origin. He was admitted to hospital aged 68 after a fall, and a ruptured spleen was removed at laparotomy. Histological analysis of the spleen suggested Niemann-Pick disease, which was subsequently confirmed. He deteriorated and died of bronchopneumonia shortly afterwards: subdural haemorrhage with storage material in neurones was found at necropsy. This late onset case of Niemann-Pick disease with neurovisceral storage is unusual and may represent a variant.

Age Factors↗

Identification of oestrogen receptors in cells of paraffin-processed breast cancers by IGSS.

Oestrogen receptor (ER) analysis of breast cancers by the standard dextran coated charcoal (DCC) method and the oestrogen receptor immunocytochemical assay (ERICA), shows that ERICA is more sensitive. We find that the immunogold-silver staining technique (IGSS), which is used on paraffin sections, is applicable to the ERICA antibody and that the DCC and IGSS methods have comparable sensitivity. Reasons for wishing to develop an improved method for oestrogen receptor localisation in paraffin sections and its advantages are given.

Breast Neoplasms↗

Tissue responses to hyperoxia. Biochemistry and pathology.

An animal model was established to study the toxic effects of hyperoxia and the consequent changes in intracellular antioxidant status. Superoxide dismutase, catalase and glutathione peroxidase activities were measured in erythrocytes, liver and lung, in addition to cellular glutathione concentrations and its associated metabolism. Overt cellular damage was assessed biochemically by measurement of lipid peroxidation, hydrogen peroxide-induced haemolysis and osmotic fragility. Pathological changes were assessed by light and electron microscopy. Up to 11 days exposure of rats to 80% oxygen was not lethal, but resulted in overt cellular damage to red blood cells (haemoglobin concentration decreased from 13.8 +/- 1.4 (SD) g dl-1 to 12.4 +/- 0.5 g dl-1; hydrogen peroxide-induced haemolysis increased from 7.7 +/- 1.6% to 75.1 +/- 13.5% after 11 days of hyperoxia) and to cells of lung (4-fold increase in lipid peroxidation) as well as a biochemical adaptation to the increased concentration of oxygen metabolites (superoxide dismutase increased 3-fold, catalase 5-fold and glutathione peroxidase 2-fold). It is suggested that red cell hydrogen peroxide-induced haemolysis and reduced glutathione concentration may be useful indicators of oxidant stress in the clinical situation.

Animals↗

Morphometric studies of age related changes in normal human breast and their significance for evolution of mammary cancer.

Ageing changes in the normal human female breast were studied to determine their significance for the evolution of mammary cancer. Employing the morphometric techniques of point counting and planimetry, objective quantitative measurements were made of the structure of the normal female breast in 58 subjects from the prepubertal to late postreproductive period. The relative amounts of epithelial and connective tissue varied with age, and the epithelial elements (combined lobular and extralobular) were unevenly distributed within the gland, with lower containing more than upper quadrants. The upper outer quadrant, however, usually contained the largest proportion of lobular units, which may relate to the higher incidence of lobular carcinoma found in this quadrant. Involution was shown to be a premenopausal rather than postmenopausal phenomenon. Mammary dysplastic changes were uncommon in all age groups.

Adolescent↗

The significance of intraduct appearances in breast cancer.

Metastatic mammary carcinomas in axillary nodes have been found to show histological appearances indistinguishable from intraduct carcinoma in breast. Since invasive breast carcinoma may mimic intraductal growth, some cases of breast cancer diagnosed histologically as intraduct carcinoma may in reality be invasive.

Axilla↗

Surface membrane staining of immunoglobulins in paraffin sections of non-Hodgkin's lymphomas using immunogold-silver staining technique.

The immunogold-silver staining (IGSS) method is a new immunostaining technique with much enhanced sensitivity for demonstration of antigens in paraffin sections. A series of 10 non-Hodgkin's lymphomas of B cell type were stained for surface membrane immunoglobulins by the IGSS and peroxidase-antiperoxidase (PAP) methods using paraffin sections and polyclonal primary antisera. The resulting staining patterns were compared with those obtained using frozen sections of the same tissues, monoclonal antibodies and the immunoperoxidase technique. The IGSS method gave a clear demonstration of surface membrane immunoglobulins in neoplastic lymphocytes using paraffin sections and the pattern of staining achieved was comparable to that obtained by the immunoperoxidase technique employing frozen sections and monoclonal antibodies. PAP staining of paraffin sections consistently failed to demonstrate the presence of any surface membrane immunoglobulin. The IGSS method provides a new approach to the diagnosis of B cell lymphomas in which routinely fixed and processed tissues may be employed to demonstrate monoclonality.

Adult↗

Immunogold-silver staining: new method of immunostaining with enhanced sensitivity.

A new method for demonstrating antigens in paraffin sections of formol sublimate-fixed tissue is described that utilizes an "indirect" immunohistological technique employing immunoglobulin adsorbed to colloidal gold as the secondary antiserum. The gold particles introduced to antigenic sites are revealed by a silver precipitation reaction. This technique, the immunogold-silver staining method, is of much enhanced sensitivity (up to 200-fold) as compared with standard immunoperoxidase and immunogold staining methods. The results have been confirmed in a study of immunoglobulins in reactive human tonsil. The use of this new method for double immunolabeling is also described.

Animals↗

Multiple pleural biopsy with the Abrams needle.

Multiple pleural biopsies (up to 10) were taken with the Abrams needle through a single aspiration site in 55 patients with pleural effusions. A definite positive or suggestive pleural biopsy diagnosis was made in 33 patients (60%). In 32 of the 33 patients the pathological abnormality was confined to only a proportion of the biopsies. Pleural biopsies were positive or suggestive in 26 out of 36 patients (72%) eventually shown to have tumour and seven out of eight patients (88%) with tuberculosis. Small pneumothoraces occurred in four patients and surgical emphysema in two.

Adult↗

Some biological characteristics of transplantable lines of mouse adenocarcinomas of the colon.

During a 5-year period colon tumors induced by 1,2-dimethylhydrazine dihydrochloride treatment in NMRI mice were transplanted sc into isologous mice to obtain transplantable tumor lines that might serve as experimental models for human colon cancer. The resultant 17 serially transplantable tumor lines were adenocarcinomas varying in degree of differentiation and mucin production. Two of the lines passaged for 5 years and used in chemotherapy studies have shown histologic progression toward dedifferentiation with concomitant acceleration of growth rate.

Adenocarcinoma↗

Cytological study of fluid from breast cysts.

A series of 215 patients with breast cysts have provided 348 specimens of cyst fluid for cytological diagnosis. Only one of these specimens was reported positive for malignant cells and this patient had a carcinoma. Nine specimens were reported as suspicious, but none of these patients had or subsequently developed carcinoma. In 338 specimens cytology was negative. A total of 178 patients (294 specimens) was available for follow-up. Of these 2 proved to have carcinomas on immediate follow-up, i.e. a lump presisted after aspiration, and a further 2 patients developed cancers in the same breast, one 4 and the other 7 years after aspiration. We therefore conclude that the routine submission of breast cyst fluid for cytology is wasteful of time and resources.

Biopsy, Needle↗