title: Cell proliferation, measured as flow cytometric S-phase fraction, is a strong prognostic indicator in FIGO stage I endometrioid endometrial carcinoma: a population-based study.
abstract: BACKGROUND
  In early-stage endometrial carcinoma, there is controversy regarding the prognostic value of the flow cytometric variables DNA ploidy (diploid vs. aneuploid) and S-phase fraction. In Sweden, the former is included in national guidelines despite poor scientific support and the latter is not used clinically. This study investigates the prognostic properties of these variables, together with classical histopathological variables, in multivariate analysis in a stringently stratified material.
  
  
  METHODS
  Consecutive, population-based patient material restricted to International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I endometrioid endometrial carcinoma (n = 1140) was retrospectively collected from routinely reported data from medical records. Data on age, FIGO stage, degree of differentiation, S-phase fraction, DNA ploidy status, and adjuvant treatment were included in the study. Cumulative incidence curves with other causes of death as a competing risk were used for univariable analysis for the primary endpoint endometrial cancer death. Cox proportional hazards regression analysis was used for multivariate modeling of all endpoints, and for univariable analysis for the secondary endpoints overall survival and time to progression.
  
  
  RESULTS
  An S-phase fraction value of >5.5% was associated with worse outcome (for endometrial cancer death: hazard ratio 2.25; 95% CI 1.38-3.67; p = 0.001, adjusted) and DNA ploidy status was not, for all endpoints tested.
  
  
  CONCLUSIONS
  In FIGO stage I endometrioid endometrial carcinoma, DNA ploidy status had no prognostic value, whereas the S-phase fraction may be used to identify those with a higher risk of adverse clinical outcome.
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Rasmus W
authors.initials: RW
authors.lastname: Green
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Sanna
authors.initials: S
authors.lastname: Engblom
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Baldetorp
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden.|Regional Cancer Center South, Region Skåne, Lund, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Hartman
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden.|Department of Clinical Pathology, Laboratory Medicine Scania, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Måsbäck
authors.affiliation: Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden.|Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjurberg
mesh_terms: D000368:Aged; D018269:Carcinoma, Endometrioid / Q000401:mortality* / Q000503:physiopathology; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000401:mortality* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D016196:S Phase; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm
keywords: Adjuvant therapy; S-phase fraction; aneuploidy; cell proliferation; endometrial neoplasm; flow cytometry; prognosis