Abstract

Cathepsin D(CD) is an intralysosomal aspartyl protease that is important in the pracess of breast carcinoma invasion and metastases by virtue of its proteolytic function, degradation of extracellular matrix, and tumar cell proliferation. Some studies have found significant correlations between increased tumor CD levels and reduced disease-free and overall survival. Other studies, however, have not found a consistent association between CD expression and prognosis. Immunohistochemical staining with Ki-67 monoclonal antibody is the best method to measure cell proliferation in breast carcinoma and its relationship to prognosis. To investigate a prognostic utility of CD and Ki-67 proliferating index(MIB-1) in breast carcinoma, 50 cases of breast carcinoma were studied for CD expression and Ki-67 proliferating index and compared them to other prognostic factors, such as estrogen receptor status, lymph node status, nuclear grade, tumor size, and mean microvessel density. Immunohistochemical staining was performed on 50 formalin-fixed, paraffin-embedded breast carcinoma tissues using a standard avidin-biotin complex method with CD(Dako) and MIB-l(Immunotech). In our series of breast carcinoma, overall CD expression was <10 % in 17 cases (34%) and was >10% in the remaining 33 cases (66%). The percentage of total CD-positive cells contributed by carcinoma cells (percent carcinoma) was <50% in 36 (72% and >50% in 14 (28%), and the percentage contributed by stromal elements(percent stroma) was >10% in 43 cases (86%). The percentage of MIB-1 expression was 0% in 5 cases, <10% in 18 cases, 10-50% in 22 cases, and >5% in 5 cases. These results showed that increased stromal CD expression significantly correlated with high nuclear grade (p< 0.05), and increased overall and carcinoma CD expression significantly correlated with tumor size (p<0.05 and p<0.02). CD expression tended to be increased in positive lymph node status, but not significant. The correlation between increased CD expression and MIB-1 proliferating index did not reach statistical significance, but there were trends to increased CD expression with increased MIB-1 proliferating index. All other prognostic factors, such as estrogen receptor status, lymph node status, and mean microvessel density, are not related with CD expression. According to these findings, a prognostic utility of CD in breast carcinoma is limited to a few prognostic factors of nuclear grade and tumor size.

• Keywords: Breast carcinoma, Cathepsin D, Ki-67(MIB-l), Prognostic factor