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Aim: To define the biological nature and malignant potential of interval cancers presenting to a breast unit within the NHS breast screening programme., Methods: 112 interval cancers were compared with matched, screen detected and symptomatic cancers in terms of their radiographic, histopathological, and immunohistochemical features., Results: Interval cancers, strictly defined, showed no characteristic radiographic pattern. In terms of size, vascular invasion, lymph node status, and prognosis they were intermediate between screen detected and symptomatic cancers. Within the interval cancers there was an excess of grade 1 and grade 3 tumours, and lesions with a high Ki67 index but immunohistochemistry otherwise failed to discriminate between the three groups. Inclusion of data from false negative "interval cancers" did not significantly alter the results., Conclusions: Interval cancers are more aggressive than screen detected cancers but in general less aggressive than symptomatic cancers. However, within a heterogeneous group, occasional interval cancers are exceptionally malignant.

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from 'clinical' cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history.

Quantification of c-erbB-2 and its relationship with other prognostic markers using flow cytometry has been examined. In this study a level for c-erbB-2 expression above which tumours are classified as positive by flow cytometry has been determined by employment of positive cut-off threshold levels. c-erbB-2 expression by both flow cytometry and immunohistochemistry was studied using the monoclonal antibody NCL-CBII. The relationship of c-erbB-2 quantification by flow cytometry was then compared with ploidy, axillary node status, tumour size and grade. Increased c-erbB-2 expression was seen using flow cytometry. Correlation between immunohistochemistry and flow-cytometry methods just failed to reach significance (P = 0.06). Immunohistochemistry revealed a significant relationship between c-erbB-2 expression and aneuploidy (P = 0.04). Cytokeratin-positive cells from 110 samples obtained from patients with breast cancer were assayed for DNA content and c-erbB-2 expression by flow cytometry. No correlation was seen between these parameters upon application of Mann Whitney analysis. However, examination of fluorescence thresholds showed a positive correlation between grade and c-erbB-2 expression at a level of more than 3200 molecules (P < or = 0.03). At the level of 3600 molecules significance was increased (P = 0.004). These levels equated with between 15% and 19% of the samples being classified as c-erbB-2-positive. Application of these cut-off points showed no correlation between c-erbB-2 expression and ploidy, tumour size or axillary node status. Comparison of ploidy and grade showed a significant association (P = 0.0015), increased grade correlating with aneuploidy.

The aim of this study was to quantify p53 expression by flow cytometry. A panel of three monoclonal antibodies: NCL-p53-240, NCL-p53-1801 and NCL-p53-DO7, was tested on breast cell lines and primary breast cancers. The relationships between ploidy, tumour grade and p53 expression for each antibody, were examined. Methodology was assessed using a variety of breast cell lines. Staining patterns were confirmed and the quantification technique qualified. Cytokeratin-positive cells from 58 samples obtained from patients with breast cancer were assayed for DNA content and p53 expression. p53 quantification was performed using calibrated fluorescent beads on cytokeratin-positive cells. Bloom and Richardson grading revealed 20 grade I and 38 grade II/III breast cancers. Examination of fluorescence thresholds showed a positive correlation between grade and DO7 (P = 0.003) at a level of 8900 molecules, 240 (P = 0.005) at a level of 2900 molecules and 1801 (P = 0.005) at a level of 1850 molecules. These levels equated with 34% (DO7), 43% (240) and 43% (1801) of the samples being classified as p53-positive. Examination of ploidy revealed 23 diploid and 35 aneuploid breast cancers. Application of p53 threshold levels on diploid and aneuploid tumours showed correlation between aneuploidy and p53 expression for DO7 at a level of 9000 molecules, 240 at a level of 1900 molecules and 1801 at a level of 1800 molecules. These levels equated with 34% (DO7), 52% (240) and 52% (1801) of the samples being classified as p53-positive. We conclude that measurement of p53 by flow cytometry may be of clinical importance by indicating levels of positivity using fluorescence thresholds. p53 expression has been shown to correlate with both grade and ploidy. Flow-cytometric measurement of p53 may be a useful prognostic assay.

Between August 1988 and July 1990, 17,678 women in the Gateshead, Sunderland, South Tyneside and Durham districts attended the national breast screening programme. A total of 131 cancers were detected. The morphology of cancers detected by screening was compared with that of tumours in 71 patients presenting clinically in the same period. Screen-detected cancers included a higher proportion of tumours of more favourable histological grade and type, were smaller in size and had less axillary lymph node involvement than those detected clinically. Survival was predicted from the Nottingham Prognostic Index. Patients with screen-detected cancer had an expected survival advantage (95 per cent confidence interval) of 26.5 (12.3-40.6) per cent at 5 years, 26.5 (11.8-41.2) per cent at 10 years and 29.1 (14.5-43.7) per cent at 15 years. This survival advantage in screened patients expected at 5, 10 and 15 years is consistent with the 30 per cent reduction in mortality rate demonstrated in the Health Insurance Plan study and the Swedish two counties trial.

Two hundred and fifty men admitted to a thoracic surgical centre and matched controls were questioned in detail about their occupations after leaving school and their smoking habits. Of 201 men with confirmed bronchial carcinoma 58 gave a history of occupational exposure to asbestos, whereas only 29 out of 201 men matched for age and residential area who were admitted with other diseases gave such a history. This difference was statistically highly significant. The usual association of bronchial carcinoma with heavy smoking was observed, but asbestos exposure increased the risk of carcinoma whatever the level of smoking. These results are consistent with the hypothesis that asbestos exposure and the level of smoking act independently in causing bronchial carcinoma. The patients with carcinoma who had been exposed to asbestos presented on average three years earlier than those who had not been exposed. Asbestos regulations have eliminated the risk of exposure to workers in scheduled industries, so asbestos-induced diseases will probably be increasingly found among the many workers who have had incidental exposure to asbestos. It is therefore important to take a full occupational history.

This case report describes three case histories and the analytical procedures used for the identification and quantification of triazolam. The levels of triazolam detected in the blood are interpreted with reference to those previously reported in the literature.

Twenty eight patients with colonic cancer, who were asymptomatic after intestinal resection and anastomosis, underwent colonoscopy as part of their routine follow up, and biopsies were obtained from the anastomosis and several other sites. Sections were stained by haematoxylin and eosin, several methods for mucin, and by the peroxidase-antiperoxidase method for carcinoembryonic antigen. Non-specific inflammatory changes were seen at the anastomosis in 11 of the 28 cases, apparent in several two years after operation; focal surface ulceration was seen in over half these samples. Neither dysplastic nor adenomatous change was detected, but at seven anastomoses the so called transitional change, which has been regarded as a preneoplastic change, was apparent. There was no consistent alteration in carcinoembryonic antigen reactivity. It is concluded that there is morphological evidence of a continued stimulus to regenerative activity at some anastomoses and that this may represent a promoting factor enhancing further carcinogenesis.

An example of chondrosarcoma developing in a patient with Ollier's disease is described. Necropsy showed an unusual pattern of multiple metastases including several within the cranial cavity.