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Biomedical subjects

J D Biggart

Publications and source records attributed to J D Biggart.

At least 19 recordsLinked to original sources

c-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma.

AIMS: To assess c-erbB-2 immunostaining in relation to morphological type of in situ and invasive breast carcinoma. METHODS: Formalin fixed, wax embedded archival tissue was used. Invasive carcinomas comprised 50 infiltrating ductal (NOS); seven medullary, 10 tubular, 15 mucinous and 24 classic invasive lobular. In situ carcinomas comprised 48 ductal (DCIS) and 10 cases of lobular (LCIS). The antibodies used were pAB1 (polyclonal) which stains cell lines that over express the c-erbB-2 oncogene, and ICR 12 (monoclonal) which stains sections of breast carcinoma known to show c-erbB-2 amplification. RESULTS: Immunostaining consistent with c-erbB-2 overexpression was found in 10 out of 50 cases of infiltrating ductal carcinoma (NOS), one of 24 infiltrating lobular carcinomas and one of seven medullary carcinomas only. Seventy per cent of ICR 12 positive cases of infiltrating ductal carcinoma also had extratumoral DCIS. Forty six per cent of pure DCIS lesions also showed strong membrane staining for c-erbB-2 protein, confined to large cell types. CONCLUSIONS: Immunostaining for c-erb B-2 oncoprotein occurs mainly in large cell DCIS and infiltrating ductal carcinoma NOS, especially those with an extratumoral DCIS component. There is a low incidence in other types of breast cancer, including those associated with a better prognosis. Different biological mechanisms may be responsible for histologically distinct types of breast carcinoma.

Breast Neoplasms

Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.

Adult

Predictive value for coeliac disease of antibodies to gliadin, endomysium, and jejunum in patients attending for jejunal biopsy.

OBJECTIVE: To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. DESIGN: Clinical assessment and laboratory analysis of patients with suspected coeliac disease. SETTING: Gastroenterology department of teaching hospital. PATIENTS: 96 adults with suspected coeliac disease attending for jejunal biopsy. MAIN OUTCOME MEASURES: Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. RESULTS: 28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. CONCLUSION: Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.

Adolescent

Pseudosarcomatous lesions of the urinary bladder.

The clinical, microscopical, immunocytochemical and ultrastructural features of five cases of benign mesenchymal proliferative lesions of the urinary bladder, mimicking sarcoma, are presented. Four of the five patients are alive and disease-free following diagnosis, an interval ranging from 9 months to 9 years, mean 4 years. A fifth patient, who had a pseudosarcomatous stromal response adjacent to a urinary transitional cell carcinoma, now has invasive transitional cell carcinoma. The lesions revealed a striking microscopical, immunocytochemical and ultrastructural similarity to nodular fasciitis, suggesting the lesions represented a bizarre mesenchymal proliferative response to inflammation.

Adult

Primary adenocarcinoma of the jejunum and ileum: clinicopathological review of 25 cases.

Between 1954 and 1988 only a total of twenty five cases of primary adenocarcinoma of the small bowel (excluding periampillary tumours) were recorded at the Department of Histopathology, Belfast City Hospital. Of these, 14 tumours were located in the jejunum: the remainder arose in the ileum. The average age at presentation was 61.3 years and a slight female to male preponderance of 1:7:1 was noted. The adenocarcinoma arose from a preexisting villous adenoma in six cases. The overall prognosis was poor, with a five year survival of 15.7%. All the survivors had tumours located in the jejunum. The single most important prognostic indicator was the depth of tumour invasion or stage at the time of diagnosis. Tumour size and grade did not seem to correlate well with survival. It is concluded that the rarity of these tumours and their inaccessibility hinder detection and treatment and that surgical resection is more effective than chemotherapy.

Adenocarcinoma

Architectural morphometry in ulcerative colitis with dysplasia.

Semi-automatic image analysis was used to assess the architectural features of normal colorectal mucosa and ulcerative colitis with and without dysplasia. Eight measured and derived morphometric variables were compared with the histological grading. The main data-set variation was due to: (1) the area of mucosa and epithelium per unit length of muscularis mucosae; (2) mean mucosal and epithelial height; and (3) the percentage epithelium and number of crypts per unit length of muscularis mucosae. Discriminant analysis using the variables mean epithelial height and mean lamina propria area per unit length of muscularis mucosae separated normals (n = 10) from high-grade dysplasia (8). The classification rule allocated low-grade dysplasia (8) to the high-grade category and 60% of regeneration cases (10) to the normal mucosa group. Scatter plots of the two discriminating variables separated normal and regenerative mucosa from dysplasia. Histological review of overlapping cases allowed redesignation of a high-grade dysplasia lesion as low grade. Architectural morphometry may be of use in assessing premalignant mucosal changes in ulcerative colitis as a guide to patient surveillance and therapy.

Colitis, Ulcerative

High iron diamine-alcian blue mucin profiles in benign, premalignant and malignant colorectal disease.

The presence of mucosal hyperplasia and sialomucin goblet cell secretion (transitional mucosa) was assessed in various benign, premalignant and malignant colorectal tissues. Transitional mucosa was seen in diverticular disease, solitary ulcer syndrome of the rectum, ischaemic and irradiation colitis and other diseases including pneumatosis coli, endometriosis, haemorrhoids and a colostomy margin. Adenocarcinomas had a sulphomucin or mixed secretion pattern with transitional features in the adjacent mucosa mucosa (18/27). Premalignant adenomatous polyps showed mixed secretion with transitional glands incorporated in the stalk and sometimes in the adjacent mucosa. Epithelium showing dysplasia secreted sulphomucins and in amounts related to its degree of differentiation. Transitional mucosa may not be a primary premalignant phenomemon. The conclusion and unifying concept is that it is a secondary event related to goblet cell immaturity. This can occur, secondary to proliferation in mucosal inflammation, ischaemia and prolapse or as a phenotypic expression of growth derived from underlying dysplastic epithelium.

Colonic Diseases

Mucin profiles in ulcerative colitis with dysplasia and carcinoma.

Mucin secretion was assessed in Crohn's colitis, in ulcerative colitis with regeneration, dysplasia and carcinoma and in non-colitic adenocarcinoma. The high iron diamine-alcian blue (HID-AB) and periodate borohydride-saponification periodic acid Schiff (PB-KOH-PAS) techniques were used to demonstrate sulphomucins and sialomucins, and O-acylated sialomucins respectively. There was mucosal hyperplasia and increased sialomucin secretion in Crohn's disease, quiescent and active ulcerative colitis. In colitis with carcinoma inflamed mucosa away from the tumour had increased sialomucins as had colitis with dysplasia. They did not differ statistically from each other or from colitic controls without cancer. Dysplastic crypts frequently secreted sulphomucins and the increased sialomucins were in transitional-like glands in the surface fronds or adjacent to the dysplasia. A comparative study of the HID-AB technique gave total correct qualitative allocation of individual quantitatively assessed crypts. Routine HID-AB staining did not aid the recognition of dysplasia in ulcerative colitis. With the PB-KOH-PAS technique colorectal adenocarcinoma showed a significant diminution in O-acylated sialomucins compared with its adjacent mucosa. Mucosal dysplasia in ulcerative colitis displayed a similar trend in O-acylated sialic acid variants, differing with respect to age-and sex-matched colitic controls. The PB-KOH-PAS technique may be of help in assessing mucin secretion in ulcerative colitis as a guide to the evolution of malignancy.

Adenocarcinoma

Classification of normal colorectal mucosa and adenocarcinoma by morphometry.

Semi-automatic image analysis was used to make a morphometrical assessment of 15 nuclear and cellular variables in normal (n = 20) and malignant (n = 30) colorectal epithelium. Principal components analysis on the matrix of correlations between variables identified four main sources of variation within the dataset. These were, in decreasing order of importance: (1) nuclear size, nuclear cytoplasmic ratio and nuclear position within the cell; (2) the variability of nuclear size; (3) nuclear elongation and polarity; (4) nuclear shape and its variation. Discriminant analysis was conducted between histologically normal mucosa (n = 10) and adenocarcinoma in ulcerative colitis (n = 20). Using stepwise variable selection, the mean nuclear cytoplasmic ratio (normal, mean 20.4 (s.d. +/- 2.0); tumour, mean 39.7 (s.d. +/- 7.0)) and the coefficient of variation of nucleus to cell apex distance (normal, mean 19.2 (s.d. +/- 7.5); tumour, mean 47.8 (s.d. +/- 9.1)) were chosen as discriminating features. They were used to derive a discriminant function which gave perfect discrimination between the two groups. Scatter plots of these two variables confirmed complete separation of normal mucosa from adenocarcinoma and provided a simple method of applying the discriminant function. Discriminatory performance did not deteriorate when the function was applied to further normals (n = 10) and adenocarcinoma (n = 10). This study highlights the descriptive differences between normal and malignant colorectal epithelium and shows that case allocation may be made to these two lesion categories using a morphometrically-derived classification rule.

Adenocarcinoma

Morphometrical analysis in ulcerative colitis with dysplasia and carcinoma.

Semi-automatic image analysis was used to assess the epithelium in ulcerative colitis with dysplasia and carcinoma. There were three main sources of variation within the dataset: (1) nuclear size, nuclear cytoplasmic ratio and nuclear stratification; (2) the variation of nuclear size; and (3) nuclear shape and polarity. Discriminant analysis chose the mean nuclear cytoplasmic ratio % and the coefficient of variation of nucleus to cell apex distance to derive a scoring system which completely separated normal mucosa (n = 20) and carcinoma (n = 30). The classification rule allocated all high grade dysplasia to the tumour category. Scores for regeneration and low grade dysplasia overlapped with each other and the normal and tumour groups. Scatter plots of the two discriminating variables showed good separation of regeneration and high grade dysplasia, and a degree of overlap with low grade dysplasia. The scatter plots allowed identification of overlapping and misallocated cases, requiring review of their histology and redesignation of the diagnosis in five cases. This study confirms quantitatively the visual criteria used in grading mucosal changes and their trend from regeneration through dysplasia to carcinoma. It underlines the necessity of assessing not only cytological but also architectural and inflammatory components when diagnosing regeneration and low grade dysplasia. Mucosal morphometry may be of use in confirming high grade dysplasia which is an indication for colectomy.

Adenocarcinoma

Immunohistochemical staining of colorectal tissues with monoclonal antibodies to ras oncogene p21 product and carbohydrate determinant antigen 19-9.

Two monoclonal antibodies were applied to benign, dysplastic, and malignant human colorectal tissues using immunohistochemical techniques on formalin fixed paraffin embedded material. RAP-5 antibody is directed against a synthetic peptide, reflecting an amino acid sequence of the ras oncogene p21 protein product. Despite using several different techniques and antibody dilutions differential staining between the various epithelial populations was not obtained. RAP-5 also showed other tissue components such as plasma cells, histiocytes, fibroblasts, smooth muscle and vascular endothelium. CA19-9 antibody recognizes an epithelial surface carbohydrate antigen originally derived from a human colorectal carcinoma cell line: it did not stain normal colorectal mucosa or adenomatous polyps, but showed focal expression of variable strength in regenerative, dysplastic, and cancerous mucosa in ulcerative colitis, and in non-colitic colorectal carcinoma. Neither antibody was found to be a reliable marker of the evolution of malignant mucosal changes, although CA19-9 may be of limited use in confirming adenocarcinoma of gastrointestinal origin.

Antibodies, Monoclonal