title: Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients--a study of the OVCAD consortium.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Molecular Oncology Group, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. dan.cacsire-castillo@meduniwien.ac.at.
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.forename: Stephan
authors.initials: S
authors.lastname: Polterauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Grimm
authors.forename: Elena Ioana
authors.initials: EI
authors.lastname: Braicu
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Sandrina
authors.initials: S
authors.lastname: Lambrechts
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
authors.forename: Eva
authors.initials: E
authors.lastname: Schuster
authors.forename: Theresia
authors.initials: T
authors.lastname: Thalhammer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.forename: Dan Cacsire
authors.initials: DC
authors.lastname: Castillo-Tong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger
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