C. C. Bird

NON-HODGKIN'S LYMPHOMA: CASE CONTROL EPIDEMIOLOGICAL STUDY IN YORKSHIRE

This paper reports the results of a case control study of non-Hodgkins 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.

DNA aneuploidy in colorectal adenomas.

The frequency of DNA aneuploidy was investigated by flow cytometry in 156 colorectal adenomas including 56 associated with 36 synchronous adenocarcinomas. Nine of 156 adenomas (6%) were DNA aneuploid. DNA aneuploidy correlated with increasing size (P less than 0.005) and histopathological type P less than 0.05) but not with dysplasia. Adenomas in associated with a synchronous adenocarcinoma did not have an increased incidence of DNA aneuploidy. Adenocarcinomas found in association with adenomas tend to have a lower incidence of DNA aneuploidy then the generality of colorectal cancers.

Hodgkin's disease: case control epidemiological study in Yorkshire.

This is the first report of a case-control epidemiological study on lymphomas and leukaemias occurring in Yorkshire during 1979-84. This paper deals with the results of the Hodgkins disease analysis comprising 248 cases and 489 controls. The results indicate support for previous work with respect to small family size and past history of infectious mononucleosis. Positive observations made in a previous pilot study are also confirmed and extended with respect to associations with certain chronic skin lesions, dental anaesthesia and familial factors. Negative associations are described with respect to X-ray exposures and cigarette smoking. It is proposed that these results fit into a general hypothesis that these conditions are the result of interaction between infectious agents and altered immunity in those persons genetically predisposed.

DNA aneuploidy in ulcerative colitis.

The prevalence of deoxyribonucleic acid (DNA) aneuploidy in 297 samples from 38 patients with ulcerative colitis of varying duration was investigated by flow cytometry. In 12 patients colitis was complicated by the development of colorectal carcinoma: one had three synchronous carcinomas. Only four of 14 carcinomas were DNA aneuploid. Deoxyribonucleic acid aneuploidy occurred focally in the colorectal mucosa in the presence and absence of carcinoma: rates of aneuploidy (67% in cancer patients and 42% in non-cancer patients), were not significantly different (chi 2 = 1.0962, p = 0.295). A higher rate of DNA aneuploidy was found in dysplastic tissues (21%) compared with non-dysplastic tissues (15%), but again these differences did not reach statistical significance (chi 2 = 1.0747, p = 0.299). Deoxyribonucleic acid aneuploidy and dysplastic change occurred more often with increasing duration of ulcerative colitis (p less than 0.001, p less than 0.005 respectively). We conclude that flow cytometric analysis of cellular DNA content should not replace present morphological methods of assessment of premalignancy in ulcerative colitis, but may be a useful adjunct in the identification of abnormal mucosa.

Intratumoral heterogeneity of DNA content in lung cancer

Heterogeneity of DNA content was analyzed in 208 samples from 20 resected lung tumors. Only one carcinoma was homogeneously diploid, but the others had DNA aneuploidy in at least some tissue samples. Eighteen tumors (90%) had varying degrees of heterogeneity of DNA content. Over half of these could have been mislabeled as diploid if the tumors had not been widely sampled. The importance of adequate sampling in assessing ploidy status of lung tumors is emphasized.

Sensitive in situ hybridisation technique using biotin-streptavidin-polyalkaline phosphatase complex.

A sensitive in situ hybridisation technique, using a biotin-streptavidin-polyalkaline phosphatase complex detection system, was successfully applied to smears of fresh cultured cells, frozen sections, and formalin fixed paraffin processed tissue: the procedure was successful for DNA-DNA hybridizations using a variety of DNA probes. The detection method is rapid, reliable, and economical producing a purplish-blue precipitate at the site of hybridisation and clearly visible by low power light microscopy.

Kinetic and physical studies of cell death induced by chemotherapeutic agents or hyperthermia.

The kinetics of three physical parameters: cell density, relative cytoplasmic viscosity and DNA stability to denaturation have been measured during the period preceding cell death induced by hyperthermia, methylprednisolone and a series of cancer chemotherapeutic agents. This series of measurements employed cultured human lymphoblastoid cells as an experimental system to establish the changes that can be observed in the early stages of cell death, prior to applying such measurements to tissue biopsies from solid human tumours. Cell death, induced by hyperthermia up to 43°C, methylprednisolone, vincristine, 5‐fluorouracil, BCNU and melphalan, showed essentially identical and reproducible changes corresponding to those which characterize programmed cell death (apoptosis). Such changes could also be observed following hyperthermia above 43°C, but reproducibility was poor and increasing damage to the cell membranes was evident. In cells treated with adriamycin or methotrexate, cell sub‐populations showing an increase in cell density were not detected. Measurements of DNA stability were readily performed by flow cytofluorometry thus allowing rapid quantitation of the fraction of cells in the early stages of cell death. Modified flow cytometric instrumentation would further allow measurement of cytoplastic viscosity as an additional parameter to indicate entry into programmed cell death. This suggests that these measurements could readily be applied to cell suspensions derived from tumour tissue biopsies for a more accurate assessment of tumour growth rate, and to allow monitoring of response to therapy in sequential tumour biopsies.

Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

Is DNA aneuploidy a good prognostic indicator in patients with advanced colorectal cancer

There is increasing evidence that abnormalities of cellular DNA within primary tumours are of prognostic significance. Deviation from the normal diploid DNA content of tumour cells has been associated with a poorer prognosis in carcinomas of the breast (Friedlander et al., 1984a), ovary (Friedlander et al., 1984b) and colon (Wolley et al., 1982). However, in the more advanced stages of malignant disease the association between DNA aneuploidy and prognosis does not appear to be so prominent (Hedley et al., 1985). With the current resurgence of interest in various forms of therapy for liver metastases from primary colorectal cancer e.g. hepatic resection, regional or systemic chemotherapy, hepatic arterial ligation and hepatic irradiation, it is of importance to assess the various prognostic factors that may influence the natural history. Several workers have identified a variety of indices which may be of use in assessing survival or for stratification within controlled clinical trials (Goslin et al., 1982; Lahr et al., 1983; Finan et al., 1985). In order to assess the value of ploidy in patients with advanced colorectal disease, we have studied a series of patients presenting with synchronous hepatic metastases from primary colorectal cancer whose survival has been documented and in whom the primary tumour was suitable for measurement of DNA content. Ploidy has then been compared with other well recognised prognostic variables. From a retrospective study of 94 patients with colorectal cancer and synchronous hepatic metastases presenting to the two major teaching centres in Leeds over the period 1976-80,46 cases, in whom the primary tumour was suitable for cellular DNA measurement, were selected. Clinical details of these patients are included in Table I. A standard proforma was completed for each patient recording personal details, symptoms and physical signs referrable to both the primary lesion and distant metastases, the results of pre-operative

Immunohistological demonstration of factors XIIIa and XIIIs in reactive and neoplastic fibroblastic and fibro‐histiocytic lesions

Factor XIII sub‐units a and s (XIII‐a and XIII‐b) have been localized previously in fibroblasts of the liver and in other tissues. An immunoperoxidase technique was used to localize these factors in benign and malignant fibroblastic and fibro‐histiocytic lesions. Positive staining was present in cells in almost all of the benign and fibro‐histiocytic lesions but was reduced in the malignant group. However, the pattern of staining was not sufficiently consistent to justify the use of the factors XIII as diagnostic markers in soft tissue neoplasia.