PROGNOSTIC-SIGNIFICANCE OF IMMUNOHISTOCHEMICAL ANALYSIS OF CATHEPSIN-D IN LOW-STAGE BREAST-CANCER

Background. Cathepsin D is an estrogen-regulated lysosomal protease th at may be overexpressed in breast cancer. Several studies based on bio chemical analysis of tumor cytosol have shown that high levels of cath epsin D are associated with poor outcome in patients with breast cance r. In contrast, a few immunohistochemical studies have shown that cath epsin D positivity in breast cancer cells indicates a favorable progno stic outcome or is of no prognostic significance. Methods. Because of the current controversy, the authors studied, using immunohistochemist ry, the distribution (0 to 3) and intensity (0 to 3) of cathepsin D in Stage I and II infiltrating ductal carcinoma of the breast from 245 p atients treated at the City of Hope National Medical Center, Duarte, C alifornia, from 1970 to 1986. A commercially available rabbit antiseru m to purified human cathepsin D and the standard avidin-biotin complex method were used. Statistical analysis was based on a combined low (0 or 2) or high (3 to 6) score. Results. A high cathepsin D score was a ssociated with Stage II disease (P = 0.007), positive lymph nodes (P = 0.019), high nuclear grade (P = 0.005), and c-erbB-2 oncogene amplifi cation (P = 0.013). Cathepsin D positivity was not an independent prog nostic indicator of disease-free survival (DFS) or overall survival (O S). In a subgroup analysis, the presence of cathepsin D had only a mod est association with predicting a shorter DFS in patients with negativ e lymph nodes (P = 0.072) or positive progesterone receptors (PR) (P = 0.086). Conclusions. Immunohistochemical analysis of cathepsin D, wit h the antiserum used in this study, is not an independent predictor of outcome in patients with breast cancer because of its strong associat ions with several well-established prognostic indicators.