title: Intraepithelial T cells and tumor proliferation: impact on the benefit from surgical cytoreduction in advanced serous ovarian cancer.
abstract: BACKGROUND
  The aim of the study was to determine whether tumor-infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction.
  
  
  METHODS
  Snap-frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3(+), CD8(+), FoxP3(+) tumor-infiltrating lymphocytes, and Ki67 expression. Kaplan-Meier survival curves were estimated and compared using a log-rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios. Interactions were modeled using recursive partitioning based on maximal prognostic differentiation.
  
  
  RESULTS
  Brisk intraepithelial CD8(+) cells (P = .035) and low Ki67 expression (P = .042) portended prolonged survival. The T-cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8(+) frequency had a 5-year survival rate of 73.3%. Patients with aggressive tumor behavior, that is, whose tumors exhibited low frequency of intraepithelial CD8(+) T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8(+) T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking.
  
  
  CONCLUSIONS
  For the first time, these novel interactions of T cells, tumor proliferation index, and surgical treatment reveal that biological prognosticators may be useful for surgical decision making in ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Adams
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Mark G
authors.initials: MG
authors.lastname: Cadungog
authors.forename: Rachel
authors.initials: R
authors.lastname: Hammond
authors.forename: Andrea
authors.initials: A
authors.lastname: Facciabene
authors.forename: Narciso
authors.initials: N
authors.lastname: Olvera
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Rubin
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes; D049109:Cell Proliferation; D018293:Cystadenoma, Serous / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D013601:T-Lymphocytes; D016896:Treatment Outcome
chemical_list: D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen