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 <or=0.75 mm, Clark invasion <II, without microscopic ulceration and without vascular invasion (4.14, 4.73, 6.15, 5.29 ng/mgp, respectively) than in the malignant melanomas of Breslow thickness >0.75 mm, Clark invasion of >or=II and <or=III, with microscopic ulceration and with vascular invasion (7.67, 7.41, 9.15, 10.35 ng/mgp, respectively). Higher CatL concentrations in early primary malignant melanomas indicate its possible involvement in the processes of early metastatic spread and its association with poor prognosis.
Stabuc
B
B
Division of Internal Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia. borut.stabuc@kclj.si
Mrevlje
Z
Z
Markovic
J
J
Stabuc-Silih
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis*; D003546:Cysteine Endopeptidases / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D012867:Skin / Q000201:enzymology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000401:mortality
D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L