Downregulation of nm-23 antimetastasis gene has been associated with
disease progression in some human tumors. NPD kinase A is the product of
the H-1 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(+) phenotypewas 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
