J Korean Surg Soc.  1997 Feb;52(2):168-182.

Prognostic Value of nm23 Protein Expression and Tumor Angiogenesis in Breast Cancer

  • 1Department of General Surgery, College of Medicine, Korea University, Korea.
  • 2Department of Pathology, College of Medicine, Korea University, Korea.


Mortality associated with human breast carcinoma is almost entirely due to subsequent cancer metastasis, but the molecular basis of this metastasis is not well established. The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in chromosome 17q22. This gene has been known to be involved in the metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. Tumor angiogenesis, the process leading to the formation of new vessels, plays a central role in tumor progression and distant metastasis. It is implicated in the phenomenon of dormant micrometastasis. This study was designed to determine the prognostic value of expression of the nm23 protein and tumor angiogenesis in breast cancer. Also, these two factors were compared with established clinicopathological prognostic factors and hormone receptors. 118 paraffin embedded surgical specimens of breast cancer were obtained from March, 1988 to February, 1994 and were selected for study. The expression of nm23 protein was studied by using immunohistochemical staining with anti-nm23/nuclear diphosphate kinase A. Tumor angiogenesis was quantified under light microscope by counting of the tumor microvessels(MVC) which were highlighted with anti-CD31 antibodies. The patient were allocated into two groups by mean number of MVC, one group was less 42 and the other was over 42. All the patients were female. The nm23 protein expression was positive in 74(63%) cases and was negative in 44(37%) cases. There was a significant correlation between nm23 protein expression and histologic grade(p=0.023). Positive expression of nm23 protein was correlated with positive estrogen(p=0.031) and progesterone receptors(p=0.001). Also Positive expression of nm23 protein was correlated with longer disease free survival(p=0.0026) and overall survival(p=0.0048). The group of MVC<42 showed better survival in overall(p=0.0195) and disease free survival(p=0.0014) than the other group of MVC>42. But the MVC and established clinicopathological prognostic factors did not show any correlation, neither with hormone status. When the nm23 protein and angiogenesis were considered together, 50 cases of negative nm23 protein and MVC<42 showed the best survival in overall(p=0.0111) and disease free survival(p=0.0114) among the four groups of each combination. In conclusion, the expression of nm23 protein and tumor angiogenesis can be used as new prognostic factors in conjunction with established other prognostic factors.


Breast cancer; Nm23 protein; Angiogenesis
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