title: The prognostic significance of tumour-stroma ratio in endometrial carcinoma.
abstract: BACKGROUND
  High tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. The aim of this study was to assess the prognostic significance of tumour-stroma ratio (TSR) in endometrial adenocarcinomas and investigate its relationship with other clinicopathological parameters.
  
  
  METHODS
  Clinicopathological and 5-year follow-up data were obtained for a retrospective series of endometrial adenocarcinoma patients (n=400). TSR was measured using a morphometric approach (point counting) on digitised histologic hysterectomy specimens. Inter-observer agreement was determined using Cohen's Kappa statistic. TSR cut-offs were optimised using log-rank functions and prognostic significance of TSR on overall survival (OS) and disease-free survival (DFS) were determined using Cox Proportional Hazards regression analysis and Kaplan-Meier curves generated. Associations of TSR with other clinicopathological parameters were determined using non-parametric tests followed by Holm-Bonferroni correction for multiple comparisons.
  
  
  RESULTS
  TSR as a continuous variable associated with worse OS (P=0.034) in univariable Cox-regression analysis. Using the optimal cut-off TSR value of 1.3, TSR-high (i.e. low stroma) was associated with worse OS (HR=2.51; 95% CI=1.22-5.12; P=0.021) and DFS (HR=2.19; 95% CI=1.15-4.17; P=0.017) in univariable analysis. However, TSR did not have independent prognostic significance in multivariable analysis, when adjusted for known prognostic variables. A highly significant association was found between TSR and tumour grade (P<0.001) and lymphovascular space invasion (P<0.001), both of which had independent prognostic significance in this study population.
  
  
  CONCLUSIONS
  Low tumour stromal content associates with both poor outcome and with other adverse prognostic indicators in endometrial cancer, although it is not independently prognostic. These findings contrast with studies on many--although not all--cancers and suggest that the biology of tumour-stroma interactions may differ amongst cancer types.
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK. um10hp@leeds.ac.uk.
authors.forename: Hannah
authors.initials: H
authors.lastname: Panayiotou
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK. n.m.orsi@leeds.ac.uk.
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Orsi
authors.affiliation: Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. Helene.h.thygesen@gmail.com.
authors.forename: Helene H
authors.initials: HH
authors.lastname: Thygesen
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK. a.wright@leeds.ac.uk.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Wright
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK. matthew.winder92@gmail.com.
authors.forename: Matthew
authors.initials: M
authors.lastname: Winder
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK. Richard.hutson@nhs.net.
authors.forename: Richard
authors.initials: R
authors.lastname: Hutson
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK. medmic@leeds.ac.uk.
authors.forename: Michele
authors.initials: M
authors.lastname: Cummings
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment