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      Immunohistochemical Analysis of nm23/NDP Kinase Expression in Human Lung Adenocarcinoma: Association with Tumor Progression in Clara Cell Type

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          Abstract

          Levels of nm23‐H1/nucleoside diphosphate kinase (NDP kinase) expression have been reported to correlate inversely with mctastatic potential in some tumors but not in others. Whether or not nm23 gene product is associated with metastatic potential in lung cancer is not clear as yet. We therefore immunohistochemically examined the expression of nm23 gene products in primary lung adenocarci‐no mas according to cytologic subtypes in order to clarify the association of its expression with the clinical features of the disease. Seventy‐two (64.9%) of the 111 lung adenocarcinomas were positive for nm23 protein. In lung adenocarcinoma of Clara cell type, high levels of nm23 expression were associated with advanced pathologic stage, positive lymph node status, and poorer prognosis (P<0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that higher levels of nm23 expression are associated with tumor progression in lung adenocarcinoma of Clara cell type.

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          Most cited references15

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          Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells.

          Reduced expression of the nm23 gene in certain rodent model systems and human breast tumors has been correlated with high tumor metastatic potential. To investigate the functional effects of nm23 expression, we have transfected a constitutive murine nm23-1 expression construct into highly metastatic K-1735 TK murine melanoma cells. TK clones expressing the exogenous nm23-1 construct exhibited a reduced incidence of primary tumor formation, significant reductions in tumor metastatic potential independent of tumor cell growth, and altered responses to the cytokine transforming growth factor beta 1 in soft agar colonization assays, compared with control-transfected TK clones. In contrast, nm23-1-transfected TK clones exhibited no significant differences in intrinsic tumor cell growth, i.e., primary tumor size in vivo, anchorage-dependent growth rate in vitro, and anchorage-independent colony formation in soft agar in vitro. The data demonstrate a suppressive effect of nm23 on several aspects of the cancer process, including tumor metastasis.
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            Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development.

            Tumour metastasis is the principal cause of death for cancer patients. We have identified the nm23 gene, for which RNA levels are reduced in tumour cells of high metastatic potential. In this report we identify the cytoplasmic and nuclear Nm23 protein, and show that it also is differentially expressed in metastatic tumour cells. We also find that the human Nm23 protein has sequence homology over the entire translated region with a recently described developmentally regulated protein in Drosophila, encoded by the abnormal wing discs (awd) gene. Mutations in awd cause abnormal tissue morphology and necrosis and widespread aberrant differentiation in Drosophila, analogous to changes in malignant progression. The metastatic state may therefore be determined by the loss of genes such as nm23/awd which normally regulate development.
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              Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis.

              The nm23 gene was identified in murine melanoma cells, in which its expression is associated with the cells' metastatic potential. Expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry. We measured nm23 mRNA in 71 patients with primary breast cancer and found variable levels of nm23 expression. The nm23 gene was expressed at higher levels in well-differentiated tumors (P less than .02). There was a significant inverse relationship between nm23 expression and nodal status (P less than .02). Expression of nm23 was positively associated with longer disease-free survival and overall survival, and the relationships were significant (P less than .002 and P less than .003, respectively). This study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype.
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                Author and article information

                Journal
                Jpn J Cancer Res
                Jpn. J. Cancer Res
                10.1111/(ISSN)1349-7006a
                CAS
                Japanese Journal of Cancer Research : Gann
                Blackwell Publishing Ltd (Oxford, UK )
                0910-5050
                1876-4673
                August 1994
                : 85
                : 8 ( doiID: 10.1111/cas.1994.85.issue-8 )
                : 840-846
                Affiliations
                [ 1 ]Department of Biochemistry, National Defense Medical College, Namiki 3–2, Tokorozawa, Saitama 359
                Author notes
                [*] [* ]To whom all correspondence should be addressed.
                Article
                CAE840
                10.1111/j.1349-7006.1994.tb02956.x
                5919568
                7928630
                66732b26-8c42-4cac-a5e2-d886d6f75f17
                History
                Page count
                References: 18, Pages: 7
                Categories
                Article
                Custom metadata
                2.0
                August 1994
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.6.9 mode:remove_FC converted:04.11.2015

                nm23/ndp kinase,immunohistochemistry,lung adenocarcinoma

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