Expression and Clinical Role of Growth Differentiation Factor-15 in Ovarian Carcinoma Effusions

Bock, Annika J. BSc*†; Stavnes, Helene T. BSc*; Kempf, Tibor MD‡; Tropè, Claes G. MD, PhD§∥; Berner, Aasmund MD, PhD*∥; Davidson, Ben MD, PhD*∥; Staff, Anne Cathrine MD, PhD†∥

International Journal of Gynecological Cancer:
doi: 10.1111/IGC.0b013e3181f7d6be
Basic Science
Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Author Information

*Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital; †Department of Obstetrics and Department of Gynecology, Oslo University Hospital, Ullevål, Oslo, Norway; ‡Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany; §Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital; and ∥The Medical Faculty, University of Oslo, Oslo, Norway.

Received May 19, 2010, and in revised form August 3, 2010.

Accepted for publication August 17, 2010.

Address correspondence and reprint requests to Ben Davidson, MD, PhD, Division of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. E-mail: bend@medisin.uio.no.

Financial acknowledgement: This study was supported by a grant from the Norwegian Cancer Society and by the Inger and Jon Fredriksen Foundation for Ovarian Cancer Research.

Annika J. Bock is the receiver of a MD/PhD student scholarship from the University of Oslo.

Copyright © 2010 by IGCS and ESGO