Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients - a study of the OVCAD consortium
1 Department of Obstetrics and Gynecology, Molecular Oncology Group, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
2 Section for Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria
3 Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany
4 Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, UZ Leuven, Herestraat 49, B-3000 Leuven, Belgium
5 Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany
6 Department of Pathophysiology, Center for Pathophysiology and Allergy Research, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
7 Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
8 Institute of Pathology, Charité University Hospital, Charitéplatz 1, D-10117 Berlin, Germany
9 Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
BMC Cancer 2013, 13:422 doi:10.1186/1471-2407-13-422Published: 17 September 2013
Epithelial ovarian cancer is one of the most lethal gynecologic malignancies. Clinicopathological factors do not permit precise prognosis and cannot provide guidance to specific treatments. In this study we assessed tumor infiltrating CD8+ T cells in association with Ki67 proliferation index and evaluated their prognostic impact in EOC samples.
CD8+ cells and Ki67 proliferation index were immunohistochemically determined on tissue microarrays including 203 primary epithelial ovarian tumors. Additionally, CD8 gene expression was assessed with RT-qPCR. Correlations were analyzed using Pearson’s correlation coefficients, ANOVA or T-test, or Fischer’s exact tests. Prognostic impact was evaluated using the Kaplan-Meier method and Cox regression model.
The density of CD8+ infiltrating lymphocytes did not correlate with tumor cell proliferation. Epithelial ovarian cancer patients with no Ki67+ cells in the tumor had a more than three times higher risk to die compared to the population with Ki67+ cells in the tumor (Hazard ratio (HR) = 3.34, 95%CI 1.59-7.04). High CD8+ cell infiltration was associated with improved overall survival (HR = 0.82, 95%CI 0.73-0.92).
The density of tumor infiltrating lymphocytes is independent of tumor cell proliferation. Ovarian cancer patients with Ki67- tumors showed a significantly reduced overall survival, presumably due to no or poor response to platinum-based chemotherapy. Moreover, the association of high densities of tumor infiltrating cytotoxic T lymphocytes with a better overall survival was confirmed.