CATHEPSIN-B, CATHEPSIN-H, AND CATHEPSIN-L AND THEIR INHIBITORS STEFIN-A AND CYSTATIN-C IN SERA OF MELANOMA PATIENTS

The levels of cathepsins (Cats) B, H, and L and their inhibitors stefi n A and cystatin C were determined in the sera of 43 patients with met astatic melanoma, in 54 patients with treated cutaneous melanoma with no evidence of metastatic disease, and in 30 healthy blood donors, usi ng quantitative ELISAs. The levels of Cats B and H and cystatin C were significantly higher within the group of metastatic melanoma patients compared with the healthy controls, The median Cat B was 4.8 versus 3 .6 ng/ml (P < 0.013), the median Cat H was 13.7 versus 4.9 ng/ml (P < 0.0001), and the median cystatin C was 470 versus 320 ng/ml (P < 0.02) . Cat H was also significantly increased within the group of melanoma patients with no metastasis, with a median of 9.6 ng/ml, Cat B was fou nd to correlate with Cat L (r = 0.36; P < 0.02) and cystatin C (r = 0. 41; P < 0.008). The serum level of Cat H was significantly increased i n patients showing no response to the chemoimmunotherapy as compared t o the level in responders, Metastatic melanoma patients with high cont ents of Cat B and Cat H experienced significantly shorter overall surv ival rates than the patients with low levels of each enzyme (Cat B: P < 0.003 and relative risk, 2.5; Cat H: P < 0.006 and relative risk, 2. 4, using medians as cutoff values), The other potential factors for pr ognosis for this group of patients revealed moderate (histological typ e and age) or no (tumor thickness, sex, and lymph node metastasis) pro gnostic significance, Similarly, no difference in survival was found f or stefin A, cystatin C, and Cat L, These results suggest that the ser um levels of Cats B and H could serve as prognostic factors for patien ts with advanced melanoma.