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N A Shepherd

Publications and source records attributed to N A Shepherd.

At least 73 records · Page 4Linked to original sources
PubMed1992

p53 expression is common in malignant mesothelioma.

The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.

Adult↗
PubMed1992

Changing pattern of gastric cancer in Oxfordshire.

This study compares the incidence rates of histologically confirmed gastric carcinoma in Oxfordshire in two five year periods (1960-64, 1984-88). Data were available for 215 patients in the first period, and 200 in the second. The overall incidence fell from 18/100,000 to 15/100,000 but when analysed for site, the incidence of antral tumours fell from 10 to 4.5/100,000. In contrast, there was an increase from 2.8 to 5.2/100,000 of tumours of the cardia. These changes were more pronounced in men. There was a marked association between smoking and tumours of the cardia (relative risk 4.5). Helicobacter pylori was associated with 37.5% of tumours in the 1960s series compared with 25% in the later series. The changing patterns of incidence of gastric carcinoma may, in part, be related to changes in smoking habits and perhaps a change in incidence of H pylori infection.

Age Factors↗
PubMed1991

14;18 translocation in primary intestinal lymphoma: detection by polymerase chain reaction in routinely processed tissue.

Chromosomal translocations involving the heavy chain immunoglobulin locus on chromosome 14 and a region on chromosome 18 encoding the bcl-2 gene [t(14;18)] are a characteristic and prevalent chromosomal abnormality in nodal malignant lymphoma, particularly follicular lymphoma. Using the polymerase chain reaction on routinely processed tissue, t(14;18) has been demonstrated in 22% of primary intestinal lymphomas, i.e. in two of nine cases of malignant lymphomatous polyposis, in four of 19 cases of polymorphic B-cell lymphoma and in one of four high-grade unclassified tumours. The findings in this study contradict those of other studies which have shown no such translocation in primary gastric and small intestinal lymphoma. The presence of t(14;18) indicates heterogeneity of molecular abnormalities within histopathologically homogeneous tumours and suggests that caution should be employed in using molecular cytogenetic data to support theories of tumour histogenesis. The low prevalence of this translocation in intestinal lymphoma makes the use of such a methodology as a primary diagnostic aid doubtful, although the technique may help to distinguish primary and secondary lymphoma and could also be used to demonstrate secondary spread.

Adult↗
PubMed1991

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S+G2+M phase fraction (flow cytometric analysis) and prognosis.

PCNA is a nuclear protein that is synthesized in late G1 and S phases of the cell cycle and is, therefore, correlated with the cell proliferative state. A new monoclonal antibody (PC10) to genetically engineered PCNA has been shown to label proliferating cells in formalin-fixed paraffin-embedded normal human tissues. Previous studies in lymphomas, using various markers of cell proliferation, have shown a strong correlation between indices of cell proliferation and histological grade. These studies have shown that within each histological subtype there is often a wide range of proliferative indices and that these may be of some prognostic significance. Thirty-one gastrointestinal lymphomas were studied. Our results show that there is a good correlation between PC10 index and histological grade of tumour (0.01 P greater than P greater than 0.001) and also a significant relationship between PC10 index and S+G2+M phase fraction as measured by flow cytometric analysis (r2 = 0.62; P less than 0.01). Twenty-three cases were available for survival analysis. In these cases a high PC10 score correlated with poor survival (P = 0.04). Based on this series, it appears that there is a significant relationship between PC10 index and histological grade, and between PC10 index and S+G2+M phase as measured by flow cytometric analysis. In addition, our results suggest that a high PC10 index is an adverse prognostic factor in primary gastrointestinal lymphoma.

Cell Cycle↗
PubMed1991

Human papillomavirus type 16 DNA in anal cancers from six different countries.

An association between anal squamous cell carcinoma and human papillomavirus (HPV) type 16 DNA has been documented in the UK. If HPV type 16 is an important aetiological factor in the development of this tumour it would be expected to occur in anal cancer tissues from other parts of the world. In this study a series of 173 anal squamous cell carcinoma tissue samples from five centres around the world have been examined by DNA hybridisation for HPV type 16 DNA sequences. HPV type 16 DNA was found in 50 of 173 (29%) of these. The prevalence of HPV associated anal squamous cell carcinoma was significantly lower in tissue from India and South Africa than in the Swiss, Polish, or Brazilian samples. HPV associated anal squamous cell carcinoma does occur in other countries and further investigations of the prevalence of these tumours in association with other HPV types are required.

Anus Neoplasms↗
PubMed1991

Pathological mimics of chronic inflammatory bowel disease.

When all of the macroscopic and microscopic features of Crohn's disease and ulcerative colitis are present, the correct diagnosis is usually made without difficulty. When some of the changes are absent, the accuracy of diagnosis is reduced. This review has outlined those diseases which feature some of these pathological changes and may masquerade as idiopathic chronic inflammatory bowel disease. Some of the pathological mimics are iatrogenic while other common diseases, such as bacterial infection, ischaemia, and diverticulosis may produce confusing histological appearances. The picture is complicated by the fact that many of these pathological imitators may themselves cause or predispose to chronic inflammatory bowel disease, or may complicate chronic inflammatory bowel disease. For example, drugs and infectious agents are recognisable causes of relapse in ulcerative colitis; Crohn's disease may cause diverticulitis in patients with diverticulosis; and lymphoma may complicate ulcerative colitis. It behooves all practising histopathologists to recognise these mimics of ulcerative colitis and Crohn's disease to ensure appropriate management for patients with inflammatory pathology of the intestines.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Epithelial-mesenchymal interactions can influence the phenotype of carcinoma metastases in the mucosa of the intestine.

In this paper we report two cases in which morphological differentiation of gastric adenocarcinoma has occurred when metastatic tumour was present within the lamina propria of the intestinal mucosa. In one case, there were metastases in the small intestinal mucosa and in the second case, in the mucosa of the appendix. The morphology of the intramucosal tumour simulated that of an adenomatous neoplasm. The recognition of this occurrence may be important in the differential diagnosis of primary and secondary adenocarcinomas of the gastrointestinal tract. The phenomenon is not only of diagnostic interest: the data presented here provide in vivo evidence that gastrointestinal carcinomas may differentiate in response to epithelial-mesenchymal interactions in a similar way to that seen in experimental models.

Adenocarcinoma↗
PubMed1990

Ki-ras oncogene mutations in non-HPV-associated anal carcinoma.

Human papillomavirus 16 (HPV 16) DNA is found in a high proportion of anal squamous cell carcinomas in whose genesis it is thought to play an important role. In addition, it can be shown to cooperate in vitro with activated ras oncogenes in cellular transformation. We have therefore screened a series of such tumours for activating mutations of the ras oncogene family using DNA amplified in vitro by the polymerase chain reaction (PCR) and a series of synthetic oligonucleotide probes. Mutations were seen in only two cases (both Ki-ras codon 12), neither of which was HPV-associated. Our results suggest that ras activation is not a common event in the genesis of these tumours and, when it does occur, it does not appear to cooperate with HPV.

Anus Neoplasms↗
PubMed1990

Clinical and pathological correlates of HPV type 16 DNA in anal cancer.

The aetiology of anal squamous cell carcinoma (SCC) has recently been associated with a sexually transmissible agent--human papillomavirus (HPV) type 16. In this study clinical and pathological data from a prospective series of 67 anal SCC collected over a three year period were compared with the HPV type 16 DNA content of these tumours to determine whether any of the clinical or histological parameters might predict HPV DNA content in a tumour specimen. Of twelve clinicopathological variables examined none was significantly correlated with HPV DNA content at the p = 0.01 level.

Adult↗
PubMed1990

Prognostic factors in anal squamous carcinoma: a multivariate analysis of clinical, pathological and flow cytometric parameters in 235 cases.

Clinical, pathological and flow cytometric parameters have been analysed by univariate and multivariate analysis to define those parameters of important prognostic influence in 235 cases of surgically treated squamous carcinoma of the anus and perianal skin. Patients had been treated by anorectal excision (166 patients) or by local excision (69). Analyses were carried out on five data sets--the two surgical subgroups, two groups distinguished by site of tumour and on all 235 patients. Univariate analysis showed many parameters to be of prognostic influence, although histological typing of tumours into the more common histological subtypes was of no prognostic value. Parameters of independent prognostic significance in multivariate analysis were those indicating depth of spread, inguinal lymph node involvement and DNA-ploidy. In this study the subdivision of the rarer types of anal canal tumour, such as mucoepidermoid carcinoma, microcystic squamous carcinoma and small cell anaplastic carcinoma, was relevant confirming that these tumours have a poor prognosis. It is now felt that surgery should not be employed as primary treatment in most cases of anal cancer and the results of this study have to be interpreted with caution when applied to patients treated with radiotherapy with or without chemotherapy. Nevertheless, our findings suggest that the most useful prognostic information can be gleaned from accurate clinical staging and an assessment of DNA-ploidy status.

Adult↗
PubMed1990

DNA hybridisation of routinely processed tissue for detecting HPV DNA in anal squamous cell carcinomas over 40 years.

To study possible changes in the incidence of human papillomavirus (HPV) associated anal squamous cell carcinomas (SCC) a simple, rapid, and sensitive technique (alkaline hydrolysis) to permit DNA hybridisation from formalin fixed, paraffin wax embedded tissue was developed. The sensitivity and specificity of the technique were established by comparison with Southern blot analysis and in situ hybridisation on the same tissue specimens. Ninety tissue specimens in a single analysis were examined using this technique. Alkaline hydrolysis was applied to fixed tissue samples which showed a two-fold increase over the past 10 years in the percentage of anal cancers containing HPV type 16 DNA when compared with the previous 30 years using 207 cases of anal cancer collected over a 40 year period. This method has several advantages over the polymerase chain reaction as it is simple, relatively inexpensive, and may be widely applied to the detection and quantification of DNA sequences, including cellular oncogenes.

Anus Neoplasms↗
PubMed1990

The pelvic ileal reservoir: pathology and pouchitis.

The creation of a pelvic ileal reservoir is associated with inflammatory changes in the reservoir mucosa. Chronic inflammation and villous atrophy are seen in most patients with both ulcerative colitis and familial adenomatous polyposis (FAP), the two prime indications for the operation. The mucosa undergoes a form of colonic metaplasia which is demonstrable by morphological, mucin histochemical, immunohistochemical and proliferation methods. Other pathological features such as mucosal ischaemia, mucosal prolapse, granulomas and pyloric metaplasia are seen in the pouch mucosa and these changes contribute to the confusion over definitions of pouchitis. The term pouchitis denotes a chronic relapsing inflammatory condition of the reservoir which occurs in 10-20% of patients and is one of the more severe long-term complications of reservoir construction. Useful definitions of pouchitis should include clinical, endoscopic and histopathological criteria. There are close associations between pouchitis and an original diagnosis of ulcerative colitis. The cause of pouchitis is currently obscure but there is evidence to suggest it may represent a recurrence of colitis in metaplastic mucosa and may provide a useful human model for colitis. The demonstration of markedly increased proliferative activity in association with colonic metaplasia has worrying connotations. However, dysplasia has not yet been described in colitic reservoirs and very few adenomas have been seen in polyposis reservoirs. Nevertheless the clinical and pathological evidence would indicate that long-term surveillance of the reservoir mucosa by endoscopy and mucosal biopsy is warranted.

Adenomatous Polyposis Coli↗
PubMed1989

Pouchitis.

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Anal Canal↗