Expression of p53 and NDP-K/nm23 in gastric carcinomas: association with metastasis and clinicopathologic parameters

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).

Expression of the nucleoside diphosphate kinase in human skin cancers: an immunohistochemical study

Expression of nucleoside diphosphate(NDP) kinase, which is homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential. However, the relationship remains controversial according to the tumor cell types and experimental system, with conflicting results from different research groups. In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer, we assessed the levels of NDP kinase expression in 9 keratoacanthomas (KAs), 26 squamous cell carcinomas (SCCs), and 25 basal cell carcinomas (BCCs) using immunohistochemistry. The expression of NDP kinase was intense in KA and SCC compared with BCC. However, the difference of NDP kinase expression between KA and SCC was not statistically significant. And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis. Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer. The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined.

Analysis of nm23 expression as a prognostic parameter in renal cell carcinoma

To identify the clinicopathological events including nm23 expression that underlies progression in renal cell carcinoma, a retrospective analysis of patients with renal cell carcinoma was performed. Ninety-eight cases of radical nephrectomies with extensive regional or para-aortic lymph node dissection were assessed for clinicopathological variables, and eighty-five cases underwent nm23/NDPK-A protein immunohistochemical staining. Significant parameters in survival were tumor size, histologic pattern, Fuhrman's nuclear grade, pathologic T(pT) stage, pathologic N stage, M stage, tumor thrombi, location of metastasis, and nm23 staining intensity. To assess the relationship with survival, the tumors with low and high nm23 expressions were compared. The fifty-nine patients with a high staining intensity had a significantly worse survival than did the twenty-six with a low staining intensity (p = 0.0015). Additionally nm23 staining intensity was correlated with tumor size, Fuhrman's nuclear grade, pT, and distant metastasis. Therefore, the immunostaining intensity of nm23 protein could be used as a prognostic parameter with an inverse correlation.