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Biomedical subjects

D S Sanders

Publications and source records attributed to D S Sanders.

At least 91 records · Page 5Linked to original sources

Classification and localisation of carcinoembryonic antigen (CEA) related antigen expression in normal oesophageal squamous mucosa and squamous carcinoma.

Using a panel of carcinoembryonic antigen (CEA) related antibodies in normal oesophageal squamous mucosa CEA expression is present on suprabasal squames localised to the cell membrane. Immunoblotting shows that this positivity is predominantly due to a glycoprotein of around 180 kDa representing CEA itself. Positivity in squamous carcinomas is confined to cells in foci of squamous differentiation. A shift from membranous localisation to predominant cytoplasmic overexpression is shown between normal and malignant squames using confocal microscopy. The recognition of an adhesive role for CEA and a role in enhancing distant metastases in those tumours expressing CEA highlights the importance of recording CEA expression and changes in subcellular distribution between normal and malignant tissues; CEA expression in oesophageal squamous mucosa has not been well recognised previously and changes in expression may prove of great significance in the spread and dissemination of squamous carcinoma.

Carcinoembryonic Antigen↗

Patterns of CEA-related antigen expression in invasive squamous carcinoma of the cervix.

The recognition of an adhesive role for the CEA-related antigens emphasizes the need for clear demonstration of the changes in CEA expression and subcellular localization between normal and neoplastic tissues. Using a panel of monoclonal and polyclonal antibodies, membranous and cytoplasmic CEA expression was seen in 50 invasive cervical squamous carcinomas in four distinct patterns dependent on tumour type and differentiation. Membranous CEA expression is a marker of differentiation in squamous carcinomas and may influence tumour behaviour and hence patient survival. Strong CEA positivity was seen on the endothelium of vessels containing tumour in ten cases where vascular metastases were prominent. Staining of these ten cases revealed concomitant sialated Lewis X positivity in tumour cells with weak endothelial positivity in three cases; cervical squamous tumour cells may localize to vascular endothelium, and hence disseminate, through specific binding of CEA and/or sialated Lewis X.

Carcinoembryonic Antigen↗

Departmental audit in histopathology.

Audit is now part of any laboratory service. Histopathology is no exception, and we have set up a system which allows us to review 4% of our specimens. These specimens are identified using a random number generator and reviewed by a consultant pathologist. Both slides and wet specimens are reviewed and graded according to a set scheme. The results from the first year of operation (1990) show a high rate of accuracy with no serious diagnostic disagreements between the auditor and the reporting pathologist. However, some errors which we would wish to prevent were detected and the audit has allowed us to take corrective measures. In our opinion, this form of audit is useful and necessary to maintain good clinical practice. The cost is considerable--histopathology is by its nature labour intensive. Recognition of this fact by health boards is essential if such systems are to continue.

Biopsy↗

Recurrent anaemia due to ischaemic colonic ulceration caused by cholesterol embolism.

We describe an elderly patient with generalized atherosclerosis who presented with recurrent iron-deficiency anaemia. He underwent right hemicolectomy which revealed ischaemic colonic ulceration caused by cholesterol embolism. Surgery appeared to be curative. Cholesterol embolism should be considered as a possible cause of unexplained gastrointestinal blood loss in the elderly.

Aged↗

Membranous expression of carcinoembryonic antigen (CEA) in the normal cervical squamous mucosa.

Using a panel of polyclonal and monoclonal antibodies to CEA-related antigens in paraffin-processed cervical biopsies, CEA and NCA expression has been demonstrated on the cell membrane of normal mature cervical squames. Cytofluorimetry of disaggregated cervical squames confirmed membranous expression and immunogold labelling of ultrathin cryostat sections localized CEA to the glycocalyx and to within cytoplasmic membrane-bound vesicles of mature squames. Immunoblotting of cervical tissue showed that most of the CEA reactivity was expressed as a glycoprotein of molecular weight around 180 k, probably CEA itself. Localization of the CEA to the cell membrane of mature cervical squames suggests a key role for these antigens in maintaining the integrity of the squamous mucosa, through the putative function of an adhesion molecule.

Carcinoembryonic Antigen↗

Epidermal growth factor receptors in the oesophagus.

The quantity and distribution of epidermal growth factor receptors (EGF-R) in oesophageal mucosa was studied in the oesophagus in order to determine its role in oesophageal disease. Fifty five biopsies were taken from different levels of the oesophagus in 25 consecutive patients undergoing endoscopy. Another group of eight patients with histologically proven Barrett's oesophagitis had a biopsy taken from the area of columnar lined oesophagus. A peripheral, membranous pattern was seen predominantly confined to the basal and immediately suprabasal cells in all of the first group of patients. In the superficial cells a few granular cytoplasmic structures were positive. All patients with Barrett's oesophagitis showed EGF-R staining of the surface epithelium. A computerised planimeter was used to determine the proportion of stained areas of squamous cells which were expressed as a percentage of the total area of squamous cells. The difference in the area of cells stained for EGF-R between normal and inflamed oesophageal mucosa (29.5% and 43.1% respectively) was significant (p less than 0.001).

Adult↗

Filamentous organisms in gastric brushings and gastric cancer diagnosis.

An association between filamentous organisms and gastric carcinoma has been reported in gastric biopsies. Review of 45 Papanicolaou-stained gastric brushing specimens revealed filamentous organisms in two cases. In both cases, gastric carcinoma was confirmed on follow-up. Cytopathologists should be aware that the identification of filamentous organisms in gastric brushings is a specific, although insensitive marker of gastric cancer.

Biopsy↗

The expression of Lewis(a) and Lewis(b) antigens reflects changes in fucosylation between normal and neoplastic cervical squamous epithelium.

Antibodies against the carbohydrate antigens Lewisa (Lea) and Lewisb (Leb) allow further investigation into the changes in fucosylation of the glycocalyx occurring during the normal and neoplastic development of cervical squamous epithelium. Lea and Leb are expressed on a broad zone of suprabasal cells in normal cervical squamous mucosa often independent of individual Lewis gene and secretor status. A proportion of Lea is expressed in sialylated form. In cervical intraepithelial neoplasia, the progressive dedifferentiation of the squamous mucosa is mirrored by loss of both Lea and Leb expression. In invasive squamous carcinomas, Lea and Leb expression is seen only on cells in areas of differentiation. The expression of Lea and Leb in normal and neoplastic cervical squamous epithelium resembles that of the Lex antigen described by us previously. The structural similarity between these antigens is highlighted and evidence for a common functional role in maintaining the integrity of squamous mucosae is discussed.

Antibodies, Monoclonal↗

Argyrophil carcinoma of the breast: a cytologic, histochemical, and ultrastructural study of a case.

Aspirate from an argyrophil carcinoma ("carcinoid") of the breast showed malignant dispersed epithelial cells. With Diff-Quik, the cytoplasm was seen to be abundant, with prominent eosinophilic granularity. The nuclei were fairly uniform, round or oval, and eccentric and had a finely stippled chromatin pattern. On histology, the tumor appeared typical for argyrophil carcinoma, and staining with Grimelius for argyrophilic granules was positive. Membrane-bound neurosecretory granules were seen on electron microscopy.

Aged↗

Expression of the 3-fucosyl N-acetyllactosamine (CD 15) antigen in normal, metaplastic, dysplastic, and neoplastic squamous epithelia.

The 3-fucosyl N-acetyllactosamine residue is the antigen recognized by the monoclonal antibody MC2. Using MC2, we demonstrated the distribution of this antigen in a variety of squamous epithelia. The antigen is expressed to a variable degree on supra-basal cells in most normal non-keratinizing squamous mucosae, with a similar distribution in metaplastic squamous epithelia; antibody-labelled latex microspheres and immunogold electron microscopy show the antigen to form part of the glycocalyx. In dysplastic and neoplastic squamous lesions, expression is reduced or absent except in cells around areas of differentiation. Prior neuraminidase treatment of sections had little effect on the amount or distribution of demonstrable antigen. Expression of this antigen by cells in non-keratinizing squamous epithelia gives an indication of cell maturity and may provide a histological marker for the grading of dysplastic and malignant squamous mucosal lesions. A possible role for these carbohydrate residues in squamous mucosal defence is discussed.

Antigens, Neoplasm↗

Expression of the CD 15 antigen is a marker of cellular differentiation in cervical intra-epithelial neoplasia (CIN).

The CD 15 antigen (3-fucosyl N-acetyllactosamine), present on the outer cell membrane of cervical squamous epithelial cells, is recognized by the monoclonal antibody MC2, which is similar to several commercially available antibodies. Staining sections of cervical biopsies with MC2 clearly demonstrates the zone of supra-basal differentiated cells in the normal squamous epithelium. Staining with MC2 also demonstrates the diminished proportion of this zone occurring with grades of CIN, reflecting progressive de-differentiation of the epithelium. In immature squamous metaplastic epithelium, absence of cytoplasmic differentiation is reflected by lack of staining. As expression of the CD 15 antigen by cervical squamous cells mirrors cytoplasmic maturity and is a marker of cellular differentiation, staining colposcopic biopsies with MC2 may aid the routine histopathological grading of CIN. A comparison is made between the staining pattern observed using MC2 with that of two commercially available antibodies (Leu M1 and Dako M1), and a possible role for the CD 15 antigen in cellular adhesion in squamous mucosae is discussed.

Antibodies, Monoclonal↗

Limited value of type III intestinal metaplasia in predicting risk of gastric carcinoma.

Endoscopic gastric biopsy specimens taken in 1976 from 174 patients were reviewed. Biopsy specimens from 44 patients showed intestinal metaplasia, and subtyping by mucin histochemistry showed that 16 were of type I, 14 of type II, and 14 of type III. Only two of these 174 patients developed gastric adenocarcinoma over the next 10 to 11 years: one with type II and one with type III intestinal metaplasia. Case notes of a separate group of 68 patients with gastric adenocarcinoma diagnosed in 1985 were reviewed for evidence of intestinal metaplasia in a previous gastric biopsy. Only two patients had previously been biopsied; one of these biopsy specimens showed type II intestinal metaplasia and the other showed no intestinal metaplasia. These findings suggest that subtyping of intestinal metaplasia in endoscopic gastric biopsy specimens is of only limited value in identifying patients at risk of gastric adenocarcinoma who require long term follow up.

Adenocarcinoma↗

Human oesophageal submucosal glands. Their detection mucin, enzyme and secretory protein content.

Human oesophageal submucosal glands may be regularly demonstrated by first exposing the oesophageal lumen to toluidine blue which reveals the duct ostia. Four types of cell were identified in the glands - mucous, subsidiary or serous, myoepithelial and oncocytes. The mucous cell contained neutral, sialated and sulphated mucins. The subsidiary cells held smaller amounts of neutral and sialated mucin, plus fucosyl residues. No lipids were detectable histochemically. ATP-ase and alkaline phosphatase were shown in the capillary endothelium. The duct epithelium showed some nonspecific esterase activity not sensitive to E 600. By immunoperoxidase techniques, the duct epithelium was shown to be rich in cytokeratin. The subsidiary cells contained lysozyme, CEA and pepsinogen. B lymphocytes composed most of the periductular lymphoid aggregates, although some T cells were found there and also intraepithelial and subepithelial in relation to the stratified squamous epithelium lining the oesophagus. Langerhans' cells were also demonstrated as intraepithelial by several techniques.

Alkaline Phosphatase↗