Overexpression of cathepsin B and urokinase plasminogen activator is associated with increased risk of recurrence and metastasis in patients with chondrosarcoma.
BACKGROUND
Deregulation of the cellular protease network has been shown to be responsible for aggressive clinical behavior in several common human malignancies. In the current study, the authors evaluated the expression patterns of proteases in patients with chondrosarcoma of bone and correlated these patterns with clinical outcome.


METHODS
The expression levels of urokinase plasminogen activator; matrix metalloproteinase types-1, -2, and -9; and cathepsins B and L were determined immunohistochemically in 114 cases of chondrosarcomas of bone and were correlated with their clinicopathologic parameters as well as with long term follow-up data.


RESULTS
Overexpression of cathepsin B was associated with a high rate of local recurrence (P = 0.006) and a decreased recurrence free survival (P = 0.005). Overexpression of urokinase plasminogen activator was associated with an increased rate of metastasis (P = 0. 013), a decreased metastasis free survival (P = 0.016), and a decreased 5-year overall survival rate (P = 0.048). The univariate Cox model showed that tumor extension into soft tissue, high histologic grade, and overexpression of cathepsin B were predictors of adverse outcome. Multivariate analysis showed only overexpression of cathepsin B and tumor extension into soft tissue to be independent predictors of local recurrence.


CONCLUSIONS
Overexpression of cathepsin B and urokinase plasminogen activator can be used to identify those patients with chondrosarcoma of bone who have an increased risk of local recurrence and distant metastases.
Häckel
C G
CG
Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany.
Krueger
S
S
Grote
H J
HJ
Oshiro
Y
Y
Hodges
S
S
Johnston
D A
DA
Johnson
M E
ME
Roessner
A
A
Ayala
A G
AG
Czerniak
B
B
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002401:Cathepsin B / Q000096:biosynthesis*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D002813:Chondrosarcoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D015331:Cohort Studies; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D002403:Cathepsins; D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D020781:Matrix Metalloproteinase 1