Expression and prognostic significance of Cathepsin L in early cutaneous malignant melanoma.

Cathepsins are papain-like lysosome cysteine proteases involved in tumor growth, invasiveness and spread, angiogenesis and alteration in immune and inflammatory responses. We investigated the differences in cathepsin L (CatL) concentrations in primary cutaneous malignant melanoma stage I and normal skin and correlated these values with well-established malignant melanoma prognostic factors. The study was performed on 36 patients (17 men and 19 women; mean age 54 years; range 21-84 years) with histological confirmed primary malignant melanomas less than 1.5 mm thick. The CatL concentrations were measured in 36 pairs of triton extracts of cytosols prepared from the tumor and adjacent normal tissue samples (matched pairs). The CatL concentrations were determined by commercially available enzyme-liked immunosorbent (ELISA) assay from KRKA (Novo Mesto, Slovenia). Significantly higher concentrations of CatL were detected in malignant melanomas than in normal surrounding skin (6.73 vs. 1.42 ng/mg total protein (mgp), p<0.001). Significant correlations between malignant melanoma and normal skin concentrations for CatL were found. The malignant melanoma CatL concentrations correlated significantly with normal skin (r=0.38; p=0.021). CatL concentrations were significantly lower (p<0.01) in the malignant melanomas of Breslow thickness 0.75 mm, Clark invasion of >or=II and

Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy.

BACKGROUND: Serum cystatin C, a cysteine protease inhibitor, has been suggested as a new marker of glomerular filtration rate (GFR). This study explored the possibility of replacing the creatinine clearance (CrCl) estimation of GFR with cystatin C in early detection of renal impairment in cancer patients on chemotherapy. METHODS: Serum creatinine and cystatin C concentrations as well as 24-h CrCl were determined simultaneously in 72 cancer patients. Among them, 60 were treated with combined chemotherapy with cisplatin (CDDP). Creatinine was determined enzymatically with a spectrophotometric method. Serum cystatin C was determined by a particle-enhanced turbidimetric immunoassay. RESULTS: Cystatin C and creatinine correlated significantly (P = 0.001) with CrCl. The correlation was significantly better for cystatin C than creatinine (r = 0.84 vs 0.74; P = 0.01). Stepwise regression analysis identified no differences for the correlations between cystatin C and CrCl in patients with or without metastases (r = 0.82 and 0.84, respectively) as well as before treatment and before the fourth cycle of chemotherapy (r = 0.70 and 0.75, respectively). A cystatin C cutoff concentration of 1.33 mg/L had 87% sensitivity and 100% specificity for detecting CrCl <78 mL/min. ROC analysis indicated that cystatin C was superior to serum creatinine for predicting CrCl <78 mL/min (P <0.04). CONCLUSIONS: Serum cystatin C is superior to serum creatinine for detection of decreased CrCl and potentially for the estimation of GFR in cancer patients independent of the presence of metastases or chemotherapy.