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Biomedical subjects

J D Davies

Publications and source records attributed to J D Davies.

At least 19 recordsLinked to original sources

Regulation of the myoblast-specific expression of the human beta-enolase gene.

The muscle-specific beta-enolase gene is expressed in proliferating adult myoblasts as well as in differentiated myotubes. Through deletion-transfection analysis, we identified a 79-base pair enhancer from the beta-enolase gene that leads to high level expression of a reporter gene in myoblasts, but not in fibroblasts. Following myoblast differentiation into myotubes, the activity of the enhancer declined, indicating that beta-enolase gene expression in myotubes is mediated by other regulators, possibly the myogenic helix-loop-helix family of transcription factors. Electrophoretic mobility shift assays indicated that proteins present in myoblast nuclear extracts specifically bind to the 3' half of the 79-base pair enhancer. This region contains an ets DNA-binding motif which is required not only for high level activity in myoblasts, but also for repressing activity in fibroblasts. Furthermore, the beta-enolase myoblast-specific enhancer shows limited similarity to the myoblast-specific enhancer associated with the human desmin gene, suggesting that gene expression in adult myoblasts may be coordinately regulated.

Animals

Apocrine adenosis: a precursor of aggressive breast cancer?

AIM: To investigate overexpression of c-erbB2, expression of the p53 protein product and proliferation rates in benign breast lesions with specific reference to apocrine adenosis. METHODS: Twenty one cases of apocrine adenosis were stained with monoclonal antibodies to p185, the protein product of the c-erbB2 oncogene, the protein product of the p53 tumour suppressor gene and to the cell cycle related protein Ki67. Three cases were associated with concomitant ductal carcinoma in situ of large cell type and two were associated with invasive tubular or cribriform carcinoma. RESULTS: Twelve (57.1%) cases showed membrane staining for c-erbB2 oncoprotein of apocrine cells within sclerosing adenosis and six (28.6%) had occasional p53 protein positive cells. One case not associated with carcinoma showed extensive staining of apocrine metaplasia outside the area of apocrine adenosis. The proliferation rate, as measured by Ki67 staining, was increased in some of the lesions and all lesions showed at least some of the cells to be in the cell cycle. CONCLUSIONS: The expression of abnormal oncogene products and increased proliferation in some of these apocrine lesions questions the supposed degenerative nature of the atypia seen in such cases and suggests that there may be an association between these lesions and large cell ductal carcinoma in situ and hence invasive carcinoma.

Adult

Digitization of microcalcifications in breast radiographs. Correlation with pathologic data.

A series of 104 nonpalpable breast lesions detected by mammograms and containing microcalcifications were studied. Intraoperative radiographs of intact and sliced specimens were assessed, followed by microscopic diagnosis on frozen sections of areas containing microcalcifications. Microcalcifications detected on mammograms and radiographs of the specimens were digitized and evaluated in accordance with morphometric parameters, including the mean surface, shape factor, bend energy, envelope surface and total surface, total number and concentration of microcalcifications. Benign disorders, atypical hyperplasia and carcinomas accounted for 47.2%, 4.8% and 48% of the tissue lesions, respectively, but the disorders were most often heterogeneous and mixed. Most, but not all, parameters significantly correlated with the three types of radiographs, although radiographs of the sliced specimens provided images of the best quality. Only two parameters, mean size and bend energy, were significantly different (P = .008, .0036) in benign and malignant lesions. It is concluded that image analysis of digitized microcalcifications in radiographs may provide quantitative data helpful in mammogram interpretation.

Breast Neoplasms

Consistency of histopathological reporting of breast lesions detected by screening: findings of the U.K. National External Quality Assessment (EQA) Scheme. U. K. National Coordinating Group for Breast Screening Pathology.

The aim of the scheme was to determine consistency of histopathological reporting in the United Kingdom National Breast Screening Programme. This external quality assessment scheme involved 51 sets of 12 slides which were circulated to 186-251 pathologists at intervals of 6 months for 3 years. Participants recorded their diagnoses on standard reporting forms, which were submitted to the U.K. National Cancer Screening Evaluation Unit for analysis. A high level of consistency was achieved in diagnosing major categories of breast disease including invasive carcinoma and the important borderline lesions, radial scar and ductal carcinoma in situ (DCIS), the latter exceeding a national target set prior to the onset of the scheme. Atypical hyperplasia (AH) was reported with much less consistency although, where it was the majority opinion, over 86% of diagnoses were of benign disorders and only 14% were of DCIS. Inconsistency was encountered in subtyping and measuring DCIS, the former apparently due to current uncertainties about classification and the latter to poor circumscription, variation in size in different sections and merging with zones of AH. Reporting prognostic features of invasive carcinomas was variable. Measurement of size was achieved with adequate consistency except in a small number of very poorly circumscribed tumours. Grading and subtyping were inconsistent although the latter was not specifically tested and will be the subject of future study. Members of the National Coordinating Group achieved greater uniformity than the remainder of the participants in all diagnostic categories, but both groups experienced similar types of problem. Our findings suggest that participation in the scheme improves diagnostic consistency. In conclusion, consistency in diagnosing invasive carcinoma and radial scar is excellent, and good in DCIS, but improvements are desirable in diagnosing atypical hyperplasia, classifying DCIS and reporting certain prognostic features of invasive tumours. Such improvements will require further research, the development of improved diagnostic criteria and the dissemination of clearer guidelines.

Breast

Hamartomas of the breast: six novel diagnostic features in three-dimensional thick sections.

Fifteen hamartomas of the breast have been studied by dissecting microscopy of thick sections at a depth of 1.0 to 2.5 mm, and by conventional 5 microns deep sections. This combined approach has revealed six distinctive features, three in the parenchymal structure and three in the connective tissue components. Ducts (invariably of penetrating or arcuate configuration) and discrete lobules, neither of which are seen in lesions accepted as fibroadenomas, were invariably found. In one-third of hamartomas, up to 10% of the surface area was occupied by Herãti-style nodules composed of concentric rings of epithelium. In the hyaline interlobular connective tissue characteristic drifts of caraway seed-like fibrocytes, encasement of adipocytes by hyaline collagen, or spider-naevus vascular abnormalities were found in approximately half of the mammary hamartomas when examined in thick sections. Hitherto the positive diagnosis of hamartomas of the breast has relied on a combined clinical, radiological and pathological assessment. We suggest that the additional features described here, taken in conjunction with those already known, may facilitate the recognition of mammary hamartomas by histopathological examination alone.

Adult

Nodular basement membrane deposits in breast carcinoma and atypical ductal hyperplasia: mimics of collagenous spherulosis.

Collagenous spherulosis is characterised histologically by the accumulation of hyaline globules containing basement membrane components. Originally described in the breast, it has also been found in skin and salivary gland neoplasms. In the breast it has hitherto always been associated with benign disease and reports have asserted that this is invariably the case, cautioning against the diagnosis of malignancy when the condition is seen. We present here five cases with similar appearances to collagenous spherulosis in routine histology and immunohistochemistry, and ultrastructural studies in one of them, in which the condition was not associated with simple benign breast disease. Two of the cases were associated with invasive carcinomas of unusual histological types, one with intracystic papillary carcinoma, one with comedo ductal carcinoma-in-situ and one with atypical ductal hyperplasia. We suggest that appearances similar to collagenous spherulosis can be associated, either through being formed by a lesion or by collision, with malignancy and warn that on encountering the lesions the pathologist must not assume, as suggested in previous accounts, that it denotes a benign process. This is an important observation since collagenous spherulosis is likely to be encountered more frequently in the range of lesions biopsied in national breast screening programs.

Aged

Will screening for breast cancer reduce mortality? Evidence from the first year of screening in Avon.

In the first year of screening in Avon, 93 malignant lesions were detected of which one-half were impalpable. Of the impalpable lesions, one-half were in situ or showed areas of microinvasion only. One-fifth of the malignant lesions were invasive tumours of special histological type which are known to carry a good prognosis even when not detected by screening. One-quarter of the lesions had clinical or pathological features which would be expected to confer a poor prognosis. Only 16 invasive ductal carcinomas measuring 1 cm or less in diameter were detected--a small proportion of the total number of malignant lesions. Although these early figures suggest that the effect of screening on mortality from breast cancer may be small, continued high-quality screening and careful detailed analysis are essential to determine the effect of screening on the mortality from breast cancer and the effect on the population as a whole.

Breast Neoplasms

Diagnostic and therapeutic aspects of fine-wire localization biopsy for impalpable breast cancer.

During the first 2 years (July 1989 to July 1991) of the Avon Breast Screening Service, fine-wire localization biopsy was indicated in 213 impalpable breast lesions. A total of 144 lesions were benign and 69 malignant. Only four of 213 lesions (1.9 per cent) were not excised at the first localization. Factors influencing reoperation in the 69 patients with malignant impalpable lesions were examined. There was a significant association (P < 0.001) between parenchymal disturbances on mammography and invasive carcinoma, and between non-invasive carcinoma and microcalcification (P < 0.001). In 31 patients the localization biopsy was the only surgical procedure. Thirty-eight patients required further surgery: 12 underwent further local excision and 26 mastectomy. Reoperation was more frequent in patients with calcification than in those with parenchymal disturbance (P < 0.001). The most frequent indications for mastectomy were inadequate excision of widespread comedo ductal carcinoma in situ or invasive ductal carcinoma combined with extensive ductal carcinoma in situ. Fine-wire localization biopsy was a combined therapeutic and diagnostic procedure in 31 of 69 women with impalpable screen-detected lesions. The majority of patients required further surgery because radiological abnormalities underestimated the extent of disease.

Biopsy, Needle

Failure to demonstrate the true resection margins of excised skin tumours: a case for routine marking.

A solution of silver nitrate in methanol was used to assess the demonstration of the true surgical excision margin at histology of 100 skin excisions for basal cell carcinoma. In 15% of cases the true margin was not presented and deeper sections were required. The findings highlight the need for routine marking of excision specimens of neoplastic skin lesions to prevent incorrect diagnosis of incomplete excision based on a false resection margin.

Basal Cell Carcinoma