Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.
Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols.



A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death.



A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96-6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64-8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55-7.99, P<0.00001).



Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification.
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
A C
AC
Rogers
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
D C
DC
Winter
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
A
A
Heeney
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
D
D
Gibbons
Clinical Pathology Division, Institute of Pathology, University of Bern, Bern, Switzerland.
A
A
Lugli
Department of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland.
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G
Puppa
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
K
K
Sheahan
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome