In the study of 50 matched pairs of
breast carcinoma and normal breast tissue, the activities of
cysteine proteinases (CPs),
cathepsin (Cat) B and Cat L in
tumors were increased on average by 18.5-fold and 52.5-fold respectively. The differences in activity of
cysteine proteinase inhibitors (CPIs) between
tumor and control breast tissues was also observed: in approximately two thirds of
carcinomas, lowered
CPI activity was measured (group-I patients), while similar or higher
tumor CPI activity was measured in the remaining samples (group-II patients). Relative increases in specific activity of Cat B and Cat L in group I were significantly higher than in group II. In group I more patients with histopathological
tumor grade III and negative
estrogen (ER) and
progesterone receptor (PR) levels were found, but the metastatic involvement of regional lymph nodes was similar in both groups. A 2-year follow-up study showed a significant inverse correlation between disease-free survival and increased Cat L activity, but the differences in group I and group II patients were not significant in this short time interval. In 20 matched pairs of
breast carcinoma and normal breast tissue, the mean activity of Cat D was 5.8-fold higher in
tumors compared with controls. The hypothesis that elevated Cat D activity increased CP activity and/or lowered
tumor CPI activity due to post-translational proteolytic modification appeared less likely, since no correlations between corresponding activities were observed. We suggested that lowered
CPI might rather reflect changes in transcription of intracellular CPIs, the
stefins. Immunoassay and Northern blot analysis showed that the average value of
stefin A protein and
mRNA content respectively in the majority of investigated
breast carcinoma samples were lowered, suggesting the possible value of
stefin A in diagnosis and/or prognosis of the disease.