Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion

Abstract

The expression of nucleoside diphosphate (NDP) kinase/nm23 has been reported to be inversely related to metastasizing potential of experimental cells and human breast cancer. In the present study, levels of NDP kinase/nm23 gene product in curatively resected human pancreatic adenocarcinomas were examined immunohistochemically using anti-NDP kinase antibody. Immunoreactivity for NDP kinase varied between tumors. Of 31 pancreatic tumors examined, 17 (55%; positive staining group) showed strong immunoreactivity for the NDP kinase, while 14 (45%; negative staining group) showed low or no immunoreactivity. Positive staining was associated with higher incidence of lymph node metastasis (13/17; 77%) and perineural invasion (13/17; 77%) than negative staining (5/14, 36%, P < 0.03; 4/14, 29%, P < 0.01, respectively). Positive staining was also associated with shorter overall survival and relapse-free survival than negative staining (P < 0.01, P < 0.01, respectively). No significant difference in age, sex, size, location of tumor, serum carcinoembryonic antigen (CEA) level, or histological type was found between the two groups. These results showed that, in contrast to the reports on breast cancer, NDP kinase/nm23 expression in human pancreatic cancer is positively associated with lymph node metastasis or perineural invasion and with poor prognosis. These, together with other previous reports, suggest that NDP kinase may play an important role in cancer progression or aggressiveness by altering its expression in a tissue-specific manner.

Immunohistochemical and Semiquantitative Immunoblot Analyses of Nm23-H1 and H2 Isoforms in Normal Human Tissues.

“…[19], and no correlation was found in adenocarcinoma of the lung and endometrial carcinoma [10,34]. Similarly, we found different correlations between nm23 gene expression and metastatic potential in different tumors [15,34].…”

Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells.

“…Of greater importance, nm23-transfected, highly metastatic melanoma cells exhibited reduced incidence of primary tumor formation, significant reduction in tumor metastatic potential, and altered response to transforming growth factor 31 compared with untransfected parental cells (15). However, metastatic phenotype and nm23 expression are positively correlated in pancreatic, prostatic, and ovarian carcinomas (21)(22)(23) and in neuroblastomas (24), thus raising the possibility that nm23 exerts distinct functions in different tissue types. nm23 levels correlated with proliferation in mitogen-stimulated peripheral blood lymphocytes and decreased during terminal differentiation of HL-60 cells (25).…”

Increased expression of nucleoside diphosphate kinases/nm23 in human diploid fibroblasts transformed by SV40 large T antigen or 60Co irradiation

“…The membrane was treated with affinity purified anti-rat NDP kinase rabbit polyclonal antibody (NK-2) that reacts specifically with human [24] as well as rat [23,25] NDP kinases, followed by peroxidase conjugated anti-rabbit IgG, and detection was carried out using an ECL assay kit (Amersham).…”