Analysis of cathepsin D in human breast cancer: Usefulness of the processsed 31 kDa active form of the enzyme as a prognostic indicator in node-negative and node-positive patients

The relative amounts of the precursor (52 kDa) and processed (31,27 kDa) fo rms of cathepsin D have been analyzed by Western blotting in biopsied breas t tissue cytosols from 134 lesions from invasive breast cancer patients, 24 lesions from patients with ductal carcinoma in situ (DCIS), 227 lesions fr om benign breast disease patients, and 28 lesions from normal control subje cts. The mean relative percentage amount of the 31 kDa form was significant ly increased (p < 0.001) in the invasive breast cancer group compared to th e other three groups. In addition, the mean relative percentage amount of t he 31 kDa form was significantly increased (p < 0.05) in node-positive comp ared to node-negative breast cancer patients. In the benign breast disease group, patients with proliferative-type disease had a significantly increas ed (p=0.02) mean relative percentage amount of the 31 kDa form of cathepsin D compared to patients with nonproliferative-type disease. Invasive breast cancer patients were followed for up to 75 months to determine if the rela tive percentage amount of the 31 kDa form of cathepsin D was predictive of disease-free and overall survival. Although the amount of the 31 kDa form w as not predictive of disease-free survival, patients in the 'high' 31 kDa g roup (> 18) were significantly (p < 0.05) more likely to die than patients in the 'low' 31 kDa group (less than or equal to 18%). The 12 patients who died were all node-positive and in the high 31 kDa group. It thus appears t hat the relative amount of the processed, active 31 kDa form of cathepsin D is a useful prognostic indicator, at least in node-positive breast cancer patients.