The significance of metastasis-related factors cathepsin-D and nm23 in advanced ovarian cancer.
BACKGROUND
Different regulators or effectors of the metastatic cascade can be of prognostic and/or predictive significance. Cathepsin-D and nm23 operate at different levels of the metastatic process and have not yet been analyzed in combination in ovarian cancer.


METHODS
The prevalence of cathepsin-D and nm23 expression was studied with immunohistochemistry in a cohort of 185 previously untreated cases of FIGO stage III ovarian cancer. Correlations with known prognostic factors were examined, and both uni- and multivariate survival analyses were performed.


RESULTS
Epithelial cell cathepsin-D expression was found in 58% of cases, stromal cell cathepsin-D expression in 20%, and nm23 expression in 72%. Epithelial cell cathepsin-D expression was positively correlated with better differentiation of the tumor tissue (P = 0.034). No correlation was found between epithelial and stromal cell cathepsin-D expression, but a striking degree of positive correlation was demonstrated between epithelial cell cathepsin-D and nm23 expression (P = 0.005). None of the factors studied was of any value in predicting the response to platinum and anthracyclin combination chemotherapy, as assessed by second look laparotomy. In univariate analysis age, FIGO substage, histological type, differentiation grade, ascites, residual disease and epithelial cathepsin-D were associated with corrected survival. Neither stromal cell cathepsin-D, nor nm23 expression were of prognostic significance. However, in multivariate analysis the combination of epithelial and stromal cell cathepsin-D expression (P = 0.030), residual disease (P = 0.002) and differentiation grade (P = 0.007) were the only remaining independent prognostic factors in this patient group.


CONCLUSIONS
Our results support a favourable prognostic significance of cathepsin-D expression in advanced ovarian cancer, but underscore the importance of considering both epithelial and stromal cell expression. We could not confirm the prognostic significance of nm23 expression in the present cohort of advanced ovarian cancer patients.
Baekelandt
M
M
Department of Gynecologic Oncology, Norwegian Radium Hospital, Montebello, Oslo, Norway.
Holm
R
R
Tropé
C G
CG
Nesland
J M
JM
Kristensen
G B
GB
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000556:secondary*; D002402:Cathepsin D / Q000032:analysis*; D015331:Cohort Studies; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis*; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis*
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D002402:Cathepsin D; D020559:Monomeric GTP-Binding Proteins