nm23 in ovarian cancer: correlation with clinical outcome and other clinicopathologic and biochemical prognostic parameters.

Abstract

The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients. Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody. Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles. The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.