Expression of maspin predicts poor prognosis in breast‐cancer patients

Abstract

The tumor suppressor gene maspin has been reported to inhibit the invasiveness and motility of breast cancer cells. It has been reported that maspin is expressed in normal human mammary epithelial cells but is downregulated during cancer progression, and that p53 could induce maspin expression by transcriptional activation. However, to date, the clinical significance of maspin expression and its correlation with p53 protein expression in human breast cancer patients have not been elucidated. One hundred and sixty-eight female patients diagnosed with invasive ductal carcinoma, who had undergone a mastectomy (154 patients) or breast-conserving surgery (14 patients), were followed up for 15–119 months (median: 87 months) postoperatively. Immunoreactivity for maspin and p53 antibodies with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Tumors with more than 20% of positive cells were considered positive for the expression of maspin. The expression of maspin in carcinoma cells was found in 27.4% (46 of 168) and significantly correlated with larger tumor size (p = 0.008), higher histologic grade (p = 0.0001) and positive p53 status (p = 0.003). A significant inverse relationship was observed between the expression of maspin and estrogen receptor (p = 0.0004) or progesterone receptor status (p = 0.02). Univariate analysis by log-rank test revealed a significant association between the expression of maspin and shorter relapse-free survival (p < 0.0001) and overall survival (p < 0.0001). According to Cox's multivariate analysis, the expression of maspin had the most significant effect in relapse-free survival (p < 0.0001) and overall survival (p < 0.0001) followed by lymph node status. In turn, the expression of maspin in 58 cases of ductal carcinoma in situ were also investigated to explore whether the downregulation of maspin through cancer progression are true or not. However, there were no positive cases in our series. These results seem to be contrary to previous reports defining maspin as a tumor suppressor gene. Although more precise characterization of the maspin expression, especially gene analysis is essential, the present investigation suggests that the expression of maspin is not downregulated through malignant progression and that the immunohistochemic detection of maspin in carcinoma cells may be helpful for selecting the group of breast cancer patients with an aggressive phenotype.