Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density.
OBJECTIVE
Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer.


METHODS
Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors.


RESULTS
Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05).


CONCLUSIONS
Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.
Lösch
A
A
Clinical Institute of Pathology, University of Vienna, A-1090 Vienna, Austria. peter.birner@akh-wien.ac.at
Schindl
M
M
Kohlberger
P
P
Lahodny
J
J
Breitenecker
G
G
Horvat
R
R
Birner
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002402:Cathepsin D / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D002402:Cathepsin D