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 oper ate at different levels of the metastatic process and have not yet been ana lyzed in combination in ovarian cancer. Patients and 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 wer e 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%. Epi thelial cell cathepsin-D expression was positively correlated with better d ifferentiation of the tumor tissue (P = 0.034). No correlation was found be tween epithelial and stromal cell cathepsin-D expression, but a striking de gree of positive correlation was demonstrated between epithelial cell cathe psin-D and nm23 expression (P = 0.005). None of the factors studied was of any value in predicting the response to platinum and anthracyclin combinati on chemotherapy, as assessed by second look laparotomy. In univariate analy sis 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 pro gnostic significance. However, in multivariate analysis the combination of epithelial and stromal cell cathepsin-D expression (P = 0.030), residual di sease (P = 0.002) and differentiation grade (P = 0.007) were the only remai ning independent prognostic factors in this patient group. Conclusions: Our results support a favourable prognostic significance of ca thepsin-D expression in advanced ovarian cancer, but underscore the importa nce of considering both epithelial and stromal cell expression. We could no t confirm the prognostic significance of nm23 expression in the present coh ort of advanced ovarian cancer patients.