Expression and clinical role of growth differentiation factor-15 in ovarian carcinoma effusions.

Abstract

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β family. We analyzed the expression and clinical role of GDF-15 in ovarian carcinoma effusions. The concentration of soluble GDF-15 was measured in 195 effusion supernatants from 162 patients with ovarian carcinoma by an immunoradiometric assay. Tumor cell GDF-15 expression was investigated in 114 effusions from the same patients using immunohistochemistry. Growth differentiation factor-15 was detected in all effusion supernatants by immunoradiometric assay. Growth differentiation factor-15 cytoplasmic expression in carcinoma cells was seen in 111 (97%) of 114 specimens. Effusion GDF-15 concentration correlated positively with GDF-15 tumor cell expression (P < 0.001). Growth differentiation factor-15 concentration was higher in effusions from patients who previously received chemotherapy compared with specimens from patients not treated with chemotherapy (P = 0.028). High GDF-15 effusion concentration was associated with poor response to chemotherapy at first disease recurrence (P = 0.001). In univariate survival analysis, high concentration of GDF-15 in effusions was associated with poor overall survival (P = 0.016), and this finding retained its prognostic value in Cox multivariate analysis (P = 0.01). Tumor cell expression of GDF-15 did not correlate with survival in analysis of the entire cohort. However, high tumor cell GDF-15 expression in prechemotherapy specimens was associated with poor progression-free survival (P = 0.046). Soluble GDF-15 is universally present in effusions from patients with ovarian carcinoma, and tumor cells represent a likely source for soluble GDF-15 in effusions. Growth differentiation factor-15 emerges as a potential prognostic biomarker in ovarian carcinoma.