title: Tumour budding at invasive margins and outcome in colorectal cancer.
abstract: OBJECTIVE
  Tumour budding, defined as small clusters of undifferentiated cancer cells at invasive margins, has been shown to reflect biologic aggressiveness of colorectal cancers. We therefore examined the prognostic significance of tumour budding in patients with colorectal carcinoma, particularly focusing on comparisons with other clinicopathological findings.
  
  
  METHODS
  Tumour budding was investigated in surgically resected specimens from 159 patients with colorectal carcinoma. With haematoxylin and eosin stained slides containing the entire invasive margin, the degree of tumour budding was classified into three grades: mild, <1/3 of the entire invasive margin; moderate, 1/3-2/3; marked, >2/3.
  
  
  RESULTS
  Mild tumour budding was found in 54 (34%) cases, moderate in 59 (37%) cases and marked in 46 (29%) cases. The degree of budding was linked with poor tumour differentiation, lymph node metastasis and advanced TNM stage (P < 0.001). In univariate analysis, patients with marked tumour budding [5-year cancer-related survival (CRS)/recurrence-free survival (RFS), 39%/53%] had significantly worse survival [CRS, hazard ratio (HR), 4.561; 95% confidence interval (CI), 2.265-9.184; P < 0.001; RFS, HR, 3.240; 95% CI, 1.430-7.342; P = 0.005] than those with mild (5-year CRS/RFS, 80%/82%) or moderate (63%/66%) budding. In the Cox regression model, marked tumour budding (HR, 3.137; 95% CI, 1.517-6.487; P = 0.002) and advanced tumour stage (stage III, HR, 3.226; 95% CI, 1.475-7.053; P = 0.003; stage IV, HR, 24.443; 95% CI, 10.843-55.100; P < 0.001) proved to be an independent predictor of short CRS.
  
  
  CONCLUSIONS
  Tumour budding is a practical and significant histological index for identification of high malignant potential and poor outcome in patients with colorectal carcinoma.
authors: Department of Surgery, National Hospital Organization Sagamihara Hospital, Sagamihara, Kanagawa, Japan.
authors: H
authors: H
authors: Kanazawa
authors: H
authors: H
authors: Mitomi
authors: Y
authors: Y
authors: Nishiyama
authors: I
authors: I
authors: Kishimoto
authors: N
authors: N
authors: Fukui
authors: T
authors: T
authors: Nakamura
authors: M
authors: M
authors: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001707:Biopsy, Needle; D015331:Cohort Studies; D003082:Colectomy / Q000009:adverse effects / Q000379:methods*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D018365:Neoplasm, Residual; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D046888:Tissue Array Analysis