Immunohistochemical Analysis of nm23 Protein in Infiltrating Ductal Carcinoma of the Breast

ABSTRACT

The nm23 gene was originally identified from murine melanoma cell lines of varying metastatic potential. A strong association has been observed between reduced expression of nm23 gene and acquisition of metastatic behavior in some tumor cells including breast cancer and melanoma, but not in others such as colon cancer, neuroblastoma, and cervical cancer. It was proposed that nm23 may function as a suppressor gene for tumor metastasis. It has recently been found that the sequence of nm23 and NDP-kinase(NDP-K) was identical. Mortality associated with human breast carcinoma is almost entirely due to subsequent metastasis, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. The purpose of this study was to investigate the relationship of nm23 protein expression with axillary lymph node metastasis and other prognostic factors. Using an immunohistochemical technique and employing a polyclonal antibody to nm23 protein, we have determined nm23 expression in a series of 72 infiltrating ductal carcinomas of the breast. Immunostaining for the nm23 gene product have heterogenous cytoplasmic and nuclear staining in 61 patients(84.7%). Sections were scored according to relative abundance(1 = less than 25% of the cells, 2 = 26-75%, 3 = 76-100%). In 61 patients with positive immunostaining, the staining was scored as 1 in 41.6%, 2 in 18.0%, and 3 in 40.2%. The staining of tumor cells was greater than that in normal epithelial cells and stromal cells. No relationship was found between nm23 expression and lymph node metastasis, histologic grade, tumor size, estrogen receptors or progesterone receptors. Therefore, nm23 protein is increased in neoplastic tissues but no correlation with metastatic potential could be demonstrated. The biological mechanism of over-expression of nm23 in malignant cells and its role in tumor progression remain to be determined.