Immunohistochemical evaluation of cathepsin D in normal, hyperplastic and malignant endometrium: Correlation with hormone receptor status c-erbB-2, p53, Rb proteins and proliferation associated indices

The immunohistochemical expression of cathepsin D was performed in paraffin embedded tissue from 79 endometrial carcinomas, 35 cases of hyperplasia, and 32 normal endometrium using the streptavidin-biotin method to investigate the role of cathepsin D (CD) in these lesions and its possible relationship with other potential and established prognostic markers. The association between CD and the other markers was assessed by univariate analysis. Tumor cell CD expression was lower in the group of carcinomas compared to the normal proliferative (P = 0.022) and secretory endometrium (P = 0.0005). In addition, hyperplastic cell CD expression was lower compared with epithelial cell CD expression in the secretory phase of normal endometrium (P = 0.009). Malignant cell CD expression was inversely correlated with tumor stromal cells (P = 0.007). A positive relationship of stromal cell CD expression with pRb (P = 0.046) and PCNA score (P < 0.0001) was detected in the group of carcinomas. In the proliferative phase of normal endometrium, epithelial CD expression was positively correlated with estrogen status (P = 0.015). The data show that down-regulation of CD expression is an early event in endometrial carcinogenesis. In addition, stromal cell CD expression may be involved in cell growth process in endometrial carcinomas.