title: Tumour budding is a reproducible index for risk stratification of patients with stage II colon cancer.
abstract: OBJECTIVE
  High-risk patients with Stage II colon cancer may benefit from adjuvant chemotherapy, but it is difficult to identify such a patient group. A robust and reproducible index would be helpful to select the subset of Stage II colon cancer patients at high risk. This study investigated the potential prognostic significance of tumour budding in Stage II colon cancer.
  
  
  METHODS
  In all, 135 Stage II colon cancer patients with known outcome were identified. The degree of tumour budding was assessed by two individual observers and was classified, according to the number of tumour buds in the area with the greatest budding intensity on haematoxylin and eosin slides, as high-grade budding (10 or more tumour buds) and low-grade budding (0-9 buds). Inter-observer agreement for two observers was assessed by using the kappa test. Progression-free and cancer-specific survivals were analysed using the Kaplan-Meier method and Cox regression.
  
  
  RESULTS
  The 5-year progression-free survival rates for patients with high-grade tumour budding (n = 36) and those with low-grade budding (n = 99) were 57.6% and 89.0% (P < 0.001). The 5-year cancer-specific survival rates were 66.7% vs 92.0% (P < 0.001). Cox regression analyses demonstrated tumour budding as an independent predictor of disease progression (hazard ratio 4.982, P < 0.001) and cancer-related death (hazard ratio 4.142, P = 0.003). The two observers agreed on the classification of tumour budding in 118 cases (87.4%) and the inter-observer agreement was good (κ = 0.692).
  
  
  CONCLUSIONS
  Tumour budding is a strong and reproducible prognostic factor for adverse outcome in Stage II colon cancer, which may serve as a prognostic marker to identify patients with a high risk of recurrence who may benefit from adjuvant therapy.
authors.affiliation: Department of Vascular and Thyroid Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Lai
authors.forename: L-C
authors.initials: LC
authors.lastname: Wu
authors.forename: P-S
authors.initials: PS
authors.lastname: Li
authors.forename: W-H
authors.initials: WH
authors.lastname: Wu
authors.forename: S-B
authors.initials: SB
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Xia
authors.forename: X-X
authors.initials: XX
authors.lastname: He
authors.forename: L-B
authors.initials: LB
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000473:pathology*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D055815:Young Adult
keywords: Colon cancer; prognosis; recurrence risk; tumour budding