Downregulation of nm-23 antimetastasis gene has been associated with disease progression in some human tumors. NPD kinase A is the product of the H1 isotype of the nm23 gene and its value as a marker of metastatic potential is well worth investigating. The expression of the nm23-H1 gene peptide was immunohistochemically evaluated in 191 primary mammary cancer tissues. A three-step immunoperoxidase staining procedure was performed and any association of our results with several classical clinicopathologic indicators, including hormonal status and c-erbB-2 oncoprotein membrane immunoexpression, was examined. NDP kinase A-positive cytoplasmic immunolabeling was noticed in 64% of all specimens (123/191) which frequently demonstrated positive progesterone receptor (PgR) status (p = 0.001) and were furthermore characterized by high PgR immunoreactivity rates. This association was significant by both univariate and multivariate statistical analysis. The double nm23-H1 (+)/PgR(+) phenotype was more frequently detected than any other combined phenotype of these markers. The nm23-H1 gene peptide was generally detected in a remarkable proportion of malignant cells, either in the invasive or the intraductal tumor components. Notably, large-cell ductal carcinomas in situ were characterized by lower nm23-H1 immunoreactivity rates when compared with other in situ cancer types. Quantitatively increased nm23-H1 immunopositive staining was more frequently observed in special histologic types of infiltrating cancers, in high nuclear grade tumors, as well as in carcinomas with high PgR levels (p = 0.05). The nm23-H1 (-)/c-erbB-2(+) phenotype was more often detected in the cancers of this study than the nm23-H1(+)/c-erbB-2(+) one. The former phenotype was correlated to postmenopausal ages as well as to extensive axillary nodal involvement by univariate statistical analysis. It is noteworthy that nm23-H1(-) status, on its own, was not statistically associated either with the presence or with a high number of involved lymph nodes. On the contrary, nm23-H1 immunopositivity was, paradoxically, more frequently observed in tumors of relatively increased TN tumor stage. Tumor progression is thus more likely to depend on the c-erbB-2 gene's overexpression. Possibly, any favorable outcome in nm23-H1(+) cases might be due to the fact that they also express PgR, which is a marker of a more functionally differentiated phenotype.

The Swedish Two-County Trial is a randomized controlled study of invitation to breast cancer screening. It was initiated in late 1977. The follow-up to the end of 1998 provides results at approximately the twentieth anniversary of the trial. A significant decrease in breast cancer death among women invited to screening was published 7-8 years after randomization and at 20-year follow up there is a significant 32% reduction in mortality associated with invitation to screening. The advent of screen-film mammographic screening with the ability to detect potentially fatal tumors at an early stage provides an opportunity to study the natural history of breast cancer at an earlier phase in its development than was possible in the past. Our findings show that breast cancer is not a systemic disease at its inception, but is a progressive disease and its development can be arrested by screening. Detection of < 15 mm and lymph node negative invasive tumors will save lives and confer an opportunity for less radical treatment.Mammography is clearly a very useful tool, not only for early detection of cancers but also for successful discrimination between the highly fatal and nonfatal cancers. The four mammographic prognostic features will be presented.