int-2 amplification in breast cancer: association with decreased survival and relationship to amplification of c-erbB-2 and c-myc.

Amplification of the int-2 oncogene was measured in a series of breast tumours and related to amplification of the c-myc and c-erbB-2 oncogenes, histopathological features and relapse-free and overall survival. int-2 was amplified in 11%, c-myc in 20% and c-erbB-2 in 27% of the tumours assessed. int-2 amplification was associated with large tumour size (p < 0.05) and reduced relapse-free (p < 0.05) and overall (p < 0.0005) survival. c-myc amplification was associated with poor tumour differentiation (p < 0.05) but had no association with prognosis. c-erbB-2 amplification was associated with low levels of expression of oestrogen receptor mRNA (p < 0.05), poor tumour differentiation (p < 0.05) and shortened relapse-free (p < 0.0001) and overall survival (p < 0.0001). This is the first report of an association between amplification of the int-2 oncogene in breast tumours and a significantly increased risk of death from breast cancer, and suggests that int-2 may be useful for identifying breast-cancer patients having a poor prognosis.

Expression of the pNR-2/pS2 protein in diverse human epithelial tumours.

The pNR-2/pS2 protein is regulated by oestrogens in breast cancer cell lines. This report describes a systematic survey of pNR-2/pS2 expression in a number of common epithelial tumours. Expression was evaluated immunohistochemically in an archival series using antisera raised against the C-terminus of the pNR-2/pS2 protein. Expression of pNR-2/pS2 by malignant epithelial tumours was widespread. Intense immunohistochemical staining was found in tumour cells in a proportion of pancreatic (6/8), large intestinal (7/12), gastric (9/16) and endometrial (4/12) carcinomas. Positive staining for the pNR-2/pS2 protein was also found in both benign and malignant ovarian epithelial tumours and was very significantly associated with mucinous differentiation (P less than 0.00001). Small numbers of carcinomas of bladder (2/10) and prostate (2/7) showed less intense staining and single examples of cervical carcinoma (1/7) and lung carcinoma (1/19) stained positively. None of the renal carcinomas (0/16) examined stained positively. Positive staining showed no correlation with gender. Although there are reports of oestrogen receptor expression in most of the tumour types considered, the possibility of other regulatory influences must also be considered. The pNR-2/pS2 protein may well have a more general role in human epithelial neoplasia than hitherto realised.

Complement activation in haemodialysis: a comparison of new and re-used dialysers.

The magnitude of leucopenia and complement activation when reusing cellulose based (Cuprophan) and synthetic (polyacrylonitrile AN-69S) haemodialysis membranes as well as their modifications by the priming of the dialysers with fresh frozen plasma and by the introduction of a period of stagnation during haemodialysis were studied using radioimmunoassay (C3a), centrifugal analysis (C3d), immunochemical (C3, Factor B) and functional (CH50 and alternate pathway) assays. Our findings demonstrate that complement activation and leucopenia induced by Cuprophan are linked and are modified when the membrane is reused, or primed with plasma protein. However, chemical exposure during reuse to sodium hypochlorite modifies these observations. Reuse of the AN-69S membrane resulted in no modification of either leucopenia or complement activity, but this membrane consistently demonstrated lower levels of C3a than observed with either first use or reused Cuprophan membranes.

Haemodialysis-induced activation of complement. Effects of different membranes.

The ability of cellulose-based (Cuprophan, saponified cellulose ester) and synthetic (polyacrylonitrile, polycarbonate, polymethylmethacrylate) haemodialysis membranes to activate complement during treatment was compared, using functional, immunochemical, radioimmunoassays, and fast centrifugal analysis assay techniques. Cellulosic and synthetic membranes show a striking similarity in their complement activation when measured by immunochemical assays. Functional haemolytic assays for alternate pathway and CH50 demonstrate no significant differences from predialysis values. C3d levels were also unable to demonstrate differences between the membranes. C3a levels, on the other hand, demonstrated significant differences between cuprophan, polyacrylonitrile, and polymethylmethacrylate but not between Cuprophan and polycarbonate membranes. Since comparable alternate-pathway activity of both cellulosic and synthetic membranes was demonstrated, but their C3a release differed, it is possible that certain surfaces that activate complement also possess the ability to absorb components of the alternate pathway.