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D S Sanders

Publications and source records attributed to D S Sanders.

At least 73 records · Page 4Linked to original sources
PubMed1999

Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours.

AIMS: Compelling evidence from cell culture studies implicates cadherins in the neoplastic progression of melanocytic tumours but few reports describe the expression of cadherins and the related transmembrane proteins, catenins, in a full range of benign and malignant excised melanocytic tumours. METHODS: Using immunohistochemistry and western blotting after tissue fractionation, the pattern of expression of cadherins/catenins was studied in a range of surgically excised melanocytic tumours, from dysplastic naevi to stage III cutaneous metastatic malignant melanoma. RESULTS: Appropriate membranous expression of E-cadherins and P-cadherins is seen in dysplastic naevocytes with an epithelioid phenotype and is largely maintained with malignant transformation to radial growth phase melanoma and primary vertical growth phase malignant melanoma. Loss of membranous E-cadherin is seen in a small number of vertical growth phase melanomas only when metastasis has occurred. However, there is a concomitant dramatic loss of membranous P-cadherin expression in all melanomas at the same stage. A minority of metastatic melanomas show de novo membranous N-cadherin expression in comparison with dysplastic naevi and primary melanoma. Membranous expression of the desmosomal cadherin, desmoglein, was not seen in any tumour studied. Frequently, beta catenin is aberrantly produced in the cytoplasm of cells in dysplastic naevi and metastatic malignant melanoma, with an implied compromise to adhesive function. Furthermore, membranous gamma catenin expression was not seen in any of the 70 melanocytic tumours studied, implying obligatory transmembrane binding of cadherins to beta catenin for maintenance of adhesive function. CONCLUSIONS: The most important alterations in membranous cadherin and catenin expression are seen late in the biological progression of melanocytic tumours at the stage of "in transit" or regional lymph node metastasis, with implications for tumour growth, invasion, and dissemination.

Blotting, Western↗
PubMed1999

Lewis blood group and CEA related antigens; coexpressed cell-cell adhesion molecules with roles in the biological progression and dissemination of tumours.

The Lewis blood group and carcinoembryonic antigen (CEA) related antigens have adhesive functions in human tissues, with roles in embryonic sorting and migration of cells (organogenesis), differentiation and protection of normal mucosal tissues, migration of neutrophils, bacterial binding, and tumour differentiation and dissemination. In the key areas of mucosal protection, neutrophil binding, and tumour metastasis, they are often coexpressed on the outer cell membrane, with Lewis blood group antigens forming the terminal carbohydrate chains on a CEA related glycoprotein backbone. The central role of these antigens in the mechanism of neutrophil binding to endothelium in inflammation highlights a fascinating paradigm for tumour cell dissemination and metastasis, and expression is linked to disease prognosis. This review outlines the structure, function, and comparative roles of these antigens in human tissues.

Carcinoembryonic Antigen↗
PubMed1998

Sequential changes in cadherin-catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma.

Maintenance of an adhesive function for cadherins requires appropriate membranous cellular expression and intact cadherin-catenin complexes. In normal squamous mucosa of the oesophagus there is membranous co-expression of E- and P-cadherin (E-cad, P-cad) in the basal compartment, whereas suprabasal stratification is associated with preservation of E-cad expression but loss of P-cad. Immunohistochemical staining of squamous dysplasia/carcinoma in situ shows a striking increase in the proportion of cells within the epithelial compartment showing co-expression of E- and P-cad with strong appropriate membranous expression of beta and gamma catenin. Strong membranous co-expression of E- and P-cad and beta catenin is seen on keratinocytes at the periphery of islands of invasive better-differentiated squamous carcinoma with keratinisation, mimicking normal mucosa. Beta catenin may be phosphorylated with implied loss of cadherin binding. Membranous cadherin and catenin expression is significantly down-regulated in poorly differentiated squamous carcinoma. No beta catenin mutations were demonstrated in squamous carcinomas following DNA extraction and sequencing, nor was any nuclear cadherin seen. Changes in cadherin-catenin complexes with cellular phenotype is well demonstrated in spindle cell carcinomas with a shift of cadherin expression from membranous to cytoplasmic between the epithelioid and spindle cell components of the tumour and with loss of expression in the sarcomatoid elements. In conclusion, we demonstrate an increased expression of P-cadherin early in tumourigenesis with loss of cadherin-catenin complexes in poorly differentiated invasive carcinomas. Cadherin/catenin expression may govern both the phenotype and biology of oesophageal squamous carcinomas.

Cadherins↗
PubMed1998

The differential diagnosis of Crohn's disease and ulcerative colitis.

Most cases of inflammatory bowel disease (IBD) can be correctly labelled as Crohn's disease (CD) or ulcerative colitis (UC) with careful initial gross and microscopic examination of biopsy and resection specimens together with close clinical and radiological correlation. Until we understand more of the aetiology and immunology of IBD we should admit that there are limitations imposed by current diagnostic criteria, consider the use of reporting proforma to improve diagnostic accuracy, and accept that in a small number of patients clinicopathological features will overlap, and CD may masquerade as UC.

Colitis, Ulcerative↗
PubMed1998

Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants.

AIMS: The staining pattern of the recently described antibody melan-A was compared with those of S100 protein and HMB-45 in a variety of melanocytic lesions to assess the specificity and sensitivity of these antibodies. METHODS AND RESULTS: Immunohistochemical staining of paraffin sections of a range of melanocytic lesions was carried out following a high temperature antigen retrieval technique. The pattern and intensity of staining was semiquantitatively scored. S100 remains the most sensitive marker of melanocytic differentiation being diffusely positive in all benign and all primary and secondary malignant lesions including naevoid melanomas, and in most desmoplastic/spindle cell melanomas. Of the two more specific melanocytic markers melan-A stains the majority of benign and malignant lesions diffusely but with occasional patchy positivity only in some secondary melanoma deposits and with little staining of desmoplastic/spindle cell melanomas. HMB-45 is the least sensitive of the three showing little positivity of benign mature naevus cells, only variable patchy positivity of primary and secondary melanoma cells and limited positivity in naevoid, desmoplastic and metastatic melanomas. CONCLUSIONS: Melan-A is a useful addition to antibody panels as it is apparently specific for melanocytic lesions and is more sensitive than HMB-45; however, it has less value than S100 in the detection of spindle cell and desmoplastic melanomas.

Antibodies, Monoclonal↗
PubMed1998

Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma.

The immunocytochemical expression of cadherins and catenins was examined during the process of oral carcinogenesis by comparing their expression in normal and dysplastic epithelium with primary and metastatic carcinomas. While control epithelium showed normal distribution for P and E cadherin and the catenins, in severe dysplasia P-cadherin was upregulated. In other cases and in carcinoma-in-situ adjacent to infiltrating carcinomas, membranous expression of the cadherins and catenins was reduced or lost. The changes in expression of E-cadherin and the catenins suggest that disruption of the E-cadherin/catenin complex is a late event associated with invasion. In primary carcinomas reduced membranous and cytoplasmic staining were observed for both cadherins and catenins. Abnormal localisation of E-cadherin occurred in the more superficial parts of the better differentiated carcinomas, suggesting abnormality to the E-cadherin complex(es). In contrast, membranous expression of cadherins and catenins was reduced or lost in the deep invasive margin of primary carcinomas and in most poorly differentiated carcinomas. For E-cadherin at least, this reduction appears associated with differentiation, invasion and possibly prognosis. Possible mechanisms involved for changes in expression of the cadherins and associated catenins and areas for further study are discussed.

Cadherins↗
PubMed1998

Ischaemic enterocolitis complicating idiopathic dysautonomia.

A previously fit 23 year old adult male who presented with a sudden onset of profound autonomic neuropathy, for which no cause could be found, is described. The patient subsequently developed ischaemic enterocolitis that ultimately necessitated colectomy and subtotal enterectomy. Potential neural and humoral mechanisms are discussed.

Acute Disease↗
PubMed1998

Alterations in classical cadherins associated with progression in ulcerative and Crohn's colitis.

Human colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. The role of cadherins, which are powerful morphoregulatory cell adhesion molecules, in colitis is provocative and as yet unknown. Herein, we present results that suggest a strong correlation between the deregulation of two cadherin molecules, E- and P-cadherins, and the progression of human colitis. We examined the expression and structural integrity of E- and P-cadherins in inflamed, dysplastic, or neoplastic human ulcerative colitis (UC) (n=58), human Crohn's colitis (n = 30), and normal tissue (n = 20) to assess cadherin function in normal and abnormal epithelium. E-cadherin is strongly expressed in normal colorectal epithelium, whereas in left-sided UC it is either down-regulated or has a single-base pair mutation in exon 4 resulting in an amino acid alteration (6 of 58 UC cases). By contrast, P-cadherin is dramatically up-regulated in both Crohn's disease and ulcerative colitis and especially in dysplastic ulcerative tissue. In vitro transfected SW-480 colorectal cells containing E-cadherin mutations identical to those in vivo were associated with increased spontaneous disaggregation compared with cells transfected with wild-type E-cadherin. Based on this evidence, we hypothesize that a small subset of colorectal cells expressing mutant E-cadherin are associated with widespread ulceration, whereas those expressing P-cadherin are associated with a rapidly dividing immature phenotype that includes dysplasia. The differential expression of mutated and wild-type cadherins examined herein are associated with a broad spectrum of abnormal epithelial phenotypes, lymphocyte integrin binding, and resistance to denudation, as is seen in the colitis adenocarcinoma sequence.

Adult↗
PubMed1997

Comparison of serum, salivary, and rapid whole blood diagnostic tests for Helicobacter pylori and their validation against endoscopy based tests.

BACKGROUND: A rapid, reliable, and accurate test for the diagnosis of infection with Helicobacter pylori is needed for screening dyspeptic patients before referral for endoscopy. AIM: To compare a new rapid whole blood test (Helisal rapid blood, Cortecs), two serum enzyme linked immunosorbent assays (ELISAs; Helico-G, Shield and Helisal serum, Cortecs), and a salivary assay (Helisal saliva, Cortecs), with slide biopsy urease, 13C-urea breath test, and histology. METHODS: Three hundred and three consecutive dyspeptic patients attending for gastroscopy underwent two antral biopsies for histology, and one for rapid slide biopsy urease test for assessment of H pylori status. Blood and saliva were also collected. One hundred of the patients also underwent a 13C-urea breath test. Gold standard positives were defined as those with at least two positive tests among slide urease, breath test, or histology, and gold standard negatives as those with all these (or two when the breath test was not done) negative. RESULTS: Of 300 patients (median age 63, range 28-89) eligible for analysis, 137 (46%) were gold standard positives, of which Helisal rapid blood identified 116, Helico-G 129, Helisal serum 130, and Helisal saliva 120; 137 (46%) were gold standard negatives of which the number falsely identified as positive was 30 by Helisal rapid blood, 45 by Helico-G, 41 by Helisal serum, and 41 by Helisal saliva. Sensitivities and specificities were: for the whole blood test 85% and 78% respectively; for Helico-G 94% and 67%, for Helisal serum 95% and 70%, and for Helisal saliva 84% and 70%. CONCLUSIONS: If endoscopy had been undertaken only on patients with positive tests two of 16 duodenal ulcers would have been missed if the Helisal rapid blood test was used, and one if any of the ELISA tests were used. None of the blood tests would have missed any of six gastric ulcers, but the salivary test would have missed one.

Adult↗
PubMed1997

Cadherin and catenin biology represent a global mechanism for epithelial cancer progression.

The cell undergoes a diverse range of stimulations including growth factor activation and signal transduction from adhesion receptors, such as cadherins. In the absence of a mitogenic signal from outside the cell, beta catenin is sequestered in complexes with the product of the adenomatous polyposis coli (APC) gene and a serine threonine glycogen kinase (GSK 3 beta) enabling degradation of free beta catenin. Residual catenins hold cells together by binding to cadherins both at adherens junctions and the actin cytoskeleton. When a mitotic signal is delivered by the wnt pathway, GSK 3 beta is antagonised so that beta catenin can no longer be degraded. Cytosolic concentrations rise and binding to other newly synthesised proteins occurs, especially transcription factors that are transported to the nucleus, such as lymphocyte enhancing factor and T cell factor. This article discusses the signalling between mitogenic and adhesion pathways and suggests that it is a global mechanism for development, differentiation, and disease. These changes in catenin and APC biology may not be sufficient alone to transform cells fully but they appear to be a necessary final common pathway for several cancers of the mucous secreting crypts (including Barrett's oesophageal lesions and colorectal cancer) or stratified secreting epithelium (melanoma) before invasion.

Cadherins↗
PubMed1996

Does palpability of primary cutaneous melanoma predict dermal invasion?

BACKGROUND: Relatively few studies have addressed the question of whether clinical estimation of melanoma thickness by palpation can accurately predict its histologic thickness. If palpability was a reliable predictor of dermal invasion, it could be used to define the surgical margin. OBJECTIVE: We sought to determine whether clinical elevation of melanoma could be used to predict the presence or absence and the degree of dermal invasion in patients with stage 1 cutaneous melanoma. METHODS: Melanomas in 165 patients were categorized by one observer as flat, just palpable, palpable, or nodular. This was compared with histologic measurements of tumor thickness. RESULTS: Overall there was significant correlation between the degree of palpability of melanoma and the presence or absence of dermal invasion (p<0.001), Breslow thickness (p<0.0001), and Clark level (p<0.001). However, the relation between palpability and Breslow thickness for invasive melanomas less than 1 mm thick was weaker (n=62, p=0.053), and the correlation between elevation and Clark level was not significant for invasive melanomas less than 4 mm thick (n=111, p>0.999). CONCLUSION: We conclude that palpability of melanoma is an inadequate guide to the presence or absence and degree of dermal invasion in melanomas less than 1 mm thick and cannot be used to determine the surgical margin.

Adolescent↗
PubMed1996

Filamentous organisms in benign and malignant gastric cytology brushings.

Review of 143 gastric brushing specimens from two centres in patients with a subsequent histological diagnosis on biopsy or gastrectomy specimens revealed filamentous organisms (FOs) in a large number of benign and malignant gastric brushings. The presence of FOs in significant numbers of brushings of benign gastric lesions contradicts the previously reported strong association of FOs with only gastric carcinoma, and questions the importance of finding these organisms in gastric brushing and biopsy material.

Bacteria↗
PubMed1995

Human piebaldism: relationship between phenotype and site of kit gene mutation.

Human piebaldism is a rare autosomal dominant disorder characterized by congenital depigmented patches of skin and hair. Piebaldism results from mutations of the kit proto-oncogene, which encodes a cell-surface receptor, tyrosine kinase, whose ligand is the stem/mast cell growth factor. We report four unrelated patients with piebaldism and consider the variations in phenotype in relation to the site of the kit gene mutation.

Adolescent↗
PubMed1995

Occult small bowel adenocarcinoma complicating Crohn's disease: a report of three cases.

Three patients with Crohn's disease are described who were treated by ileal resection for intestinal obstruction. Histological examination of the resected specimen in each case established the diagnosis of adenocarcinoma of the small intestine complicating Crohn's disease. This diagnosis should be considered in patients with longstanding macroscopic Crohn's disease who present with severe or recurrent symptoms. The diagnosis may not be apparent on routine radiological examination or even macroscopically at laparotomy.

Adenocarcinoma↗
PubMed1995

Expression of fibroblast growth factors in thyroid cancer.

We have examined immunoreactive fibroblast growth factor-1 (FGF-1) and FGF-2 in thyroid sections from normal tissue, follicular adenoma, differentiated follicular and papillary carcinoma, and anaplastic carcinoma. Polyclonal primary antibodies (Dr. A. Baird, Whittier Institute, La Jolla, CA) to FGF-1 and FGF-2 and fluorescein-conjugated secondary antibodies were used with confocal microscopy to allow quantitation and subcellular localization of the antigens. Staining for FGF-1 and FGF-2 was intense in the differentiated malignant tumor specimens, whereas staining in the normal thyroid tissue controls was not detectable above background fluorescence. Staining for FGF-1 and FGF-2 was intracellular and was not found in the nucleus. Staining using either antibody was enhanced in follicular adenomas, but was less intense than that in the malignant tumors. Sections from anaplastic carcinomas also stained positively. In primary cultures of thyroid cells derived from a papillary carcinoma, staining for FGF-2 was 10-fold greater than that from normal thyroid cells from the same patient. The data suggest a possible role for FGFs in the etiology of thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1994

Classification of CEA-related positivity in primary and metastatic malignant melanoma.

Using a panel of antibodies to carcinoembryonic antigen (CEA), in paraffin-processed biopsy material patchy, predominantly membranous positivity was seen on tumour cells in 70 per cent of cases of superficial spreading melanoma, 60 per cent of nodular melanomas, and 75 per cent of secondary deposits studied with unabsorbed polyclonal anti-CEA only. No staining was seen using monoclonal anti-CEAs. Localization of CEA to the cell membrane was confirmed with confocal microscopy. Immunoblotting of fresh frozen material detected CEA of around 180 kD in both primary and metastatic melanomas migrating with an apparent molecular weight of between 150 and 200 kD, indicating variable glycosylation of the protein. Recognition of an adhesive role for CEA with roles in immunolocalization and immunotherapy emphasizes the importance of more precise classification of CEA-related positivity in human tumours.

Carcinoembryonic Antigen↗