title: Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review and Pooled Analysis.
abstract: OBJECTIVE
  Tumour budding is defined as the presence of isolated or small clusters of malignant cells at the invasive edge of the tumour. It is considered a negative prognostic factor in colorectal cancer (CRC) and is associated with a poor outcome and adverse pathological features. Here, we report a meta-analysis of the association of tumour budding and survival in stage II CRC patients.
  
  
  METHODS
  PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that assessed the relationship between tumour budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to compute odds ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst patients with respect to the extent of tumour budding, using multivariate analysis. Data were pooled using the Mantel-Haenszel random effect model.
  
  
  RESULTS
  We analysed 12 studies that included a total of 1652 patients. High-grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 % confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5-year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly noteworthy that the presence of high-grade budding was associated with an increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001).
  
  
  CONCLUSIONS
  Tumour budding is associated with worse survival in stage II CRC, in particular in pT3N0M0 patients. It could therefore potentially be used when deciding whether to administer adjuvant chemotherapy in high-risk node negative CRC patients.
authors.affiliation: Department of Oncology, Division of Medical Oncology, Azienda Ospedaliera Treviglio, Treviglio, BG, Italy, faupe@libero.it.
authors.forename: F
authors.initials: F
authors.lastname: Petrelli
authors.forename: E
authors.initials: E
authors.lastname: Pezzica
authors.forename: M
authors.initials: M
authors.lastname: Cabiddu
authors.forename: A
authors.initials: A
authors.lastname: Coinu
authors.forename: K
authors.initials: K
authors.lastname: Borgonovo
authors.forename: M
authors.initials: M
authors.lastname: Ghilardi
authors.forename: V
authors.initials: V
authors.lastname: Lonati
authors.forename: D
authors.initials: D
authors.lastname: Corti
authors.forename: S
authors.initials: S
authors.lastname: Barni
mesh_terms: D015179:Colorectal Neoplasms / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis