Papillomaviruses and human cancer.
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Cell Transformation, Neoplastic↗
Biomedical subjects
C C Bird
Publications and source records attributed to C C Bird.
Detection of human papillomavirus in skin and genital lesions of renal allograft recipients by in situ hybridization.
Renal allograft recipients have an increased incidence of malignancy including squamous carcinoma of cervix and skin. There is growing evidence that human papillomavirus (HPV) has a part to play in malignant transformation at these sites. We have previously identified HPV DNA in the skin and genital lesions of such patients by dot and Southern blotting. In situ hybridization studies, using biotinylated DNA probes for HPV 4, 5 and 8 in skin lesions and 6, 11, 16 and 18 in genital lesions, were performed on tissues derived from the same group of patients. In the cutaneous lesions, only 25% of the specimens probed were found to contain virus by in situ hybridization; 60% of these specimens were found to harbour virus by dot and Southern blotting. In situ hybridization revealed HPV 16 and/or 18 in 86% of the genital lesions probed.
Adult↗
Sensitivity of digoxigenin and biotin labelled probes for detection of human papillomavirus by in situ hybridisation.
The sensitivity of digoxigenin and biotin labelled DNA probes for the detection of human papillomavirus (HPV) by dot blotting and in situ hybridisation was compared in tissues from cervical, laryngeal, and anogenital neoplasia. Probes were either labelled with digoxigenin by the random primer technique and detected with anti-digoxigenin antibody, or labelled with biotin by nick translation and detected with streptavidin, both methods having a common final visualisation procedure using alkaline phosphatase. Digoxigenin labelled probes proved two to 10-fold more sensitive by quantitative dot blotting and four-fold more sensitive in detecting HPV 16 DNA in a series of 31 anal carcinomas, compared with biotinylated probes. The digoxigenin method also produced less non-specific background staining of tissue sections than biotin labelled probes. It is concluded that digoxigenin DNA labelling and detection provides a simple, reliable, and efficient alternative to the use of biotin or radioactive isotopes for the detection of HPV DNA by in situ hybridisation. Digoxigenin labelled probes also offer the possibility of double labelling in situ hybridisation procedures when used with biotin labelled probes to provide simultaneous identification of different DNA sequences.
Anus Neoplasms↗
Importance of sampling method in DNA analysis of lung cancer.
Lung carcinomas are characterised by considerable histological variation within the tumour. The possible effects of this morphological heterogeneity on the estimation of tumour ploidy were investigated. Multiple tissue blocks were systematically taken from 20 lung tumours and analysed by flow cytometry. The routine, archival paraffin wax embedded diagnostic blocks from these cases were also analysed. Nineteen (95%) of the tumours were shown to contain aneuploid stemlines by systematic sampling, but if only one of these systematic tissue blocks had been taken from each case the incidence of DNA aneuploidy could have been as low as 45%. Only 15 (75%) tumours were aneuploid when all the routine archival blocks were analysed, but by specifically selecting tumour areas from the archival material the accuracy of this method was increased to 90%. It is concluded that tumour sampling methods are of primary importance in assessing the DNA content of lung tumours. Routine paraffin wax embedded archival tissue provides a suitable source of material for this purpose, provided that "turnover" selection is carried out.
Adenocarcinoma↗
Human papillomavirus in oesophageal squamous cell carcinoma.
Thirty seven cases of oesophageal squamous cell carcinoma were studied by applying DNA slot blot analysis and in situ hybridisation using type specific probes for HPV 6, 11, 16 and 18. Cases of condyloma accuminata, cervical carcinoma, and laryngeal papilloma were used as controls. Blocks including areas of invasive carcinoma, intraepithelial neoplasia, and normal epithelium were studied in each case. No HPV genome was detectable in any of the oesophageal cases. It is concluded that these types of HPV do not have an association with oesophageal squamous cell carcinoma.
Carcinoma, Squamous Cell↗
Consequences of the provision of laboratory services for the National Health Service by commercial firms: a view from the university sector.
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Education, Medical, Undergraduate↗
Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps.
Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer.
Adult↗
Chronic myeloid leukaemia in Yorkshire: a case control study.
The results of a case-control study of chronic myeloid leukaemia in adults are reported. 122 cases and 241 controls were interviewed. Excess risks associates with heart disease and related drugs were revealed. In addition a weak association with occupational and/or hobby exposure to irradiation emerged.
Case-Control Studies↗
Genetic linkage map of six polymorphic DNA markers around the gene for familial adenomatous polyposis on chromosome 5.
A genetic linkage map of six polymorphic DNA markers close to the gene (APC) for familial adenomatous polyposis (FAP) on chromosome 5q is reported. One hundred fifty-five typed members of nine FAP kindred provided more than 90 meioses for linkage analysis. A number of crucial recombination events have been identified which are informative at three or more loci, allowing confident ordering of parts of the map. There was no evidence of genetic heterogeneity, with all families showing linkage of at least one chromosome 5 marker to the gene. Recombination data and two-point linkage analysis support a locus order of centromere-pi 227-C11P11-ECB27-L5.62-APC-EF5.44-YN5.48-telomer e, although EF5.44 could lie in the interval L5.62-APC or ECB27-L5.62. No recombinants were identified between APC and either EF5.44 or YN5.48, but published deletion mapping in colorectal carcinomas and linkage analysis in FAP suggest that YN5.48 is 1-3 cM from APC. The present study suggests that YN5.48 and L5.62 delineate a small region of chromosome 5 within which the EF5.44 locus lies very close to the APC gene. These data not only allow use of flanking markers for presymptomatic diagnosis of FAP but also provide a high-density map of the region for isolation of the APC gene itself and for further assessment of the role of chromosome 5 deletions in the biology of sporadic colorectal cancer.
Adenomatous Polyposis Coli↗
Correlation of morphology, immunophenotype, and flow cytometry with remission induction and survival in high grade non-Hodgkin's lymphoma.
A series of cases of high grade non-Hodgkin's lymphomas has been studied by morphology (110 cases), immunocytochemistry (90 cases), using reagents reactive in fixed paraffin-embedded tissue, and flow cytometry (77 cases). B-cell tumours constituted 67.0 per cent of the total, T-cell tumours 22.0 per cent, and unclassified cases 8.8 per cent. Immunocytochemistry revealed two anaplastic carcinomas. Of the 77 cases studied by flow cytometry, 67.5 per cent were diploid and 32.5 per cent DNA aneuploid. T-cell tumours were more likely to be diploid than B-cell tumours, though the difference did not reach statistical significance. T-cell tumours had a significantly lower proliferative index (%S + G2) than B-cell tumours (P = 0.002). The overall remission induction rate was 68 per cent and actuarial 3-year survival 47 per cent. There was a trend for cases with %S + G2 less than 22 per cent to survive longer (P = 0.07). This trend became statistically significant when aneuploid cases were added to the high PI group (P = 0.04). No correlation was seen between morphological or immunophenotypic groups and remission induction rates or survival.
Adolescent↗
Comparison of histopathological and flow cytometric parameters in prediction of prognosis in gastric cancer.
Flow cytometric analysis was performed retrospectively on material from 76 patients having potentially curative resection for gastric carcinoma between 1968 and 1984. The prognostic significance of DNA aneuploidy was compared with that of conventional histological grading and staging of the tumour. The presence of DNA aneuploidy was associated with a significantly poorer prognosis when compared with diploid tumours (P less than 0.02), but was not found to be predictive of survival when the presence of lymph node metastases (P less than 0.0001) and resection margin involvement (P less than 0.003) were allowed for using multiple regression analysis. When intestinal and diffuse types of gastric carcinoma were analysed separately, DNA aneuploidy was associated with a significantly shorter survival only in patients with intestinal type tumours.
Adult↗
Linkage analysis in familial adenomatous polyposis: order of C11P11 (D5S71) and pi 227 (D5S37) loci at the apc gene.
Linkage analysis with DNA probes C11P11 and pi 227 is reported in six Scottish families with familial adenomatous polyposis. Two families were informative for C11P11 and all six were at least partly informative for pi 227. Two C11P11-apc and two pi 227-apc recombinants were identified and one of these was recombinant for both C11P11-apc and pi 227-apc. A further possible combined C11P11-apc and pi 227-apc recombination event was also identified. Peak lod score for linkage of C11P11 to apc was 5.80 at a recombination fraction (theta) of 0.069 (95% probability limits 0.012-0.191) and for linkage of pi 227 to apc was 3.19 at theta = 0.110 (95% probability limits 0.023-0.286). Peak lod score for linkage of C11P11 to pi 227 was 1.79 at theta = 0.00. The data support a gene order of pi 227-C11P11-apc.
Chromosomes, Human, Pair 5↗
High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21-22.
Familial adenomatous polyposis is transmitted by a gene (APC) located within 5q21-22. Hemizygous loss of at least a part of 5q has been reported in 19-36% of sporadic colorectal carcinomas. This suggests that an anti-oncogene is located on that chromosome arm, but the probes used previously gave little information on the status of APC in the tumours. Using DNA probes homologous to polymorphic sequences flanking and close to the APC locus we show that more than half of a large series of carcinomas had lost at least one flanking allele. Mapping of allele losses provides data that imply clustering of breakpoints in a 10-15 megabase region around APC. The commonest chromosome defect responsible for APC loss was interstitial deletion. Mitotic recombination or partial arm loss were less frequent mechanisms. Whole chromosome loss was rare. This pattern contrasts with that reported in acquired homozygosity at other anti-oncogene loci in sporadic tumours and implies that APC loss is an early event in colorectal carcinogenesis. This view is also supported by the observations that 5q21-22 loss occurs with similar frequency in DNA diploid and DNA aneuploid tumours, and also in tumours at all clinical stages of progression.
Adenoma↗
Teaching systemic pathology in Edinburgh.
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Curriculum↗
Non-Hodgkin's lymphoma: case control epidemiological study in Yorkshire.
This paper reports the results of a case control study of non-Hodgkin's lymphoma in the Yorkshire Health Region. In all, 437 cases and 724 controls were interviewed. Risk factors associated with past skin conditions, family history of cancer and infectious mononucleosis, aspects of social life and contact with wood dust and epoxy glues all emerge. A comparison of high and low grade morphological forms of disease reveal contrasting risks and suggest separate aetiologies for these conditions.
England↗
DNA aneuploidy and cell proliferation in familial adenomatous polyposis.
Two hundred and thirteen samples from 20 patients with familial adenomatous polyposis (FAP) were investigated by flow cytometry and the results compared with 100 sporadic adenomas. Eleven of the 20 (55%) yielded one or more DNA aneuploid samples with an overall incidence within FAP adenomas of 12%. Despite a similar level of DNA aneuploidy in sporadic adenomas, it was commonly detected at a smaller polyp size. The degree of cell proliferation was found to be similar in the two groups (median %S+G2 15.8% v 16.4%) but larger FAP adenomas demonstrated a higher level of cell proliferation than smaller adenomas. DNA aneuploidy had no value as a predictor of a synchronous carcinoma and appeared to be an early change in the development of carcinoma in these patients.
Adenomatous Polyposis Coli↗
Hodgkin's disease: a flow cytometric study.
Flow cytometry was performed on paraffin embedded tissue from 115 cases of Hodgkin's disease. Thirteen (11%) tumours were aneuploid with no significant difference between the histological subgroups. The median proliferative index was 14%, and the highest values were found in the NS2 (16.4%) and lymphocyte depleted (16.0%) subgroups. The difference in proliferative index approached significance when the NS2 subgroup was compared with the NS1 subgroup (p less than or equal to 0.11) and when the lymphocyte depleted and NS2 subgroups combined were compared with the mixed cellularity, lymphocyte predominance, and NS1 subgroups combined (p less than or equal to 0.07). There was a trend towards better survival for patients with aneuploid tumours and those cases with a proliferative index below 15%, but neither of these trends was significant.
Adolescent↗
Prognostic indicators in centroblastic-centrocytic lymphoma.
The prognostic importance of ploidy and proliferative index (%S + G2) assessed by flow cytometry, mitotic and centroblast counts, and histological growth pattern were evaluated in biopsy specimens taken before treatment from 60 cases of centroblastic-centrocytic non-Hodgkin's lymphoma. Cases with a high proliferative index (greater than or equal to 18%) or DNA aneuploidy showed significantly poorer survival than those with a low proliferative index (less than 18%). A high mitotic count was also associated with a poor prognosis. On multiple regression analysis the flow cytometric assessments and mitotic counts were significant predictors of survival. Assessments of proliferative activity clearly have prognostic potential in centroblastic-centrocytic lymphoma and may permit more accurate characterisation of individual tumours.
Adult↗