Prognostic significance of cathepsins B and L in primary human breast cancer.
OBJECTIVE
Evaluation of the clinical significance of cytosolic tumor levels of the lysosomal cysteine proteases cathepsin B (catB) and cathepsin L (catL) in patients with primary breast cancer.


METHODS
CatB (n = 1,500) and catL (n = 1,391) levels were determined by enzyme-linked immunosorbent assay (ELISA) in cytosols routinely prepared from frozen-tissue samples that were submitted to our laboratory for the assessment of steroid-hormone-receptor status. The median duration of follow-up of patients still alive at the time of analysis was 93 months.


RESULTS
Relating catB and catL levels with classical prognostic factors, the proteases were positively correlated with the number of positive lymph nodes (P < .01), and negatively with the level of steroid-hormone receptors (P < .01). We did not find a significant relationship between catB or catL levels with age and menopausal status of the patients or with the size of the primary tumor. The levels of catB and catL were positively correlated with each other and with the rates of relapse and death (all, P < .0001). In multivariate regression analysis for relapse-free survival (RFS) and overall survival (OS), corrected for the contribution of age/menopausal status, tumor size, the number of positive lymph nodes, and steroid-hormone-receptor status, catB and catL were significant predictors of the rates of relapse and death (all, P < .01). No statistically significant interactions of catB or catL with any of the classical prognostic factors or with each other were observed in their associations with the rates of relapse and death.


CONCLUSIONS
CatB and catL levels measured in routinely prepared cytosols are strong parameters to predict the rate of relapse and the length of survival after treatment of the primary breast tumor.
Foekens
J A
JA
Department of Medical Oncology, Rotterdam Cancer Institute, Dr Daniel den Hoed Kliniek/Academic Hospital Rotterdam, The Netherlands. foekens@bidh.azr.nl
Kos
J
J
Peters
H A
HA
Krasovec
M
M
Look
M P
MP
Cimerman
N
N
Meijer-van Gelder
M E
ME
Henzen-Logmans
S C
SC
van Putten
W L
WL
Klijn
J G
JG
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000401:mortality; D002401:Cathepsin B / Q000032:analysis*; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis*; D003546:Cysteine Endopeptidases; D003600:Cytosol / Q000201:enzymology; D010450:Endopeptidases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000032:analysis; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D015415:Biomarkers; D011956:Receptors, Cell Surface; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L