title: Intratumoural budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastases in colon and rectal cancer patients.
abstract: BACKGROUND
  In colorectal cancer (CRC), tumour budding at the invasion front is associated with lymph node (LN) and distant metastasis. Interestingly, tumour budding can also be detected in biopsies (intratumoural budding; ITB) and may have similar clinical importance. Here we investigate whether ITB in preoperative CRC biopsies can be translated into daily diagnostic practice.
  
  
  METHODS
  Preoperative biopsies from 133 CRC patients (no neoadjuvant therapy) underwent immunohistochemistry for pan-cytokeratin marker AE1/AE3. Across all biopsies for each patient, the densest region of buds at × 40 (high-power field; HPF) was identified and buds were counted.
  
  
  RESULTS
  A greater number of tumour buds in the biopsy was associated with pT stage (P=0.0143), LN metastasis (P=0.0007), lymphatic (P=0.0065) and venous vessel invasion (P=0.0318) and distant metastasis (cM1) (P=0.0013). Using logistic regression, a 'scale' was developed to estimate the probability of LN and distant metastasis using the number of tumour buds (e.g. 10 buds per HPF: 64% chance of LN metastasis; 30 buds per HPF: 86% chance). Inter-observer agreement for ITB was excellent (intraclass correlation coefficient: 0.813).
  
  
  CONCLUSIONS
  Tumour budding can be assessed in the preoperative biopsy of CRC patients. It is practical, reproducible and predictive of LN and distant metastasis. Intratumoural budding qualifies for further investigation in the prospective setting.
authors.affiliation: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Zlobec
authors.affiliation: Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Hädrich
authors.affiliation: 1] Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland [2] Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Dawson
authors.affiliation: 1] Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland [2] Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: V H
authors.initials: VH
authors.lastname: Koelzer
authors.affiliation: Department of Oncology, Hospital Centre Biel, Biel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Borner
authors.affiliation: 1] Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland [2] Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Mallaev
authors.affiliation: Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Schnüriger
authors.affiliation: Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Inderbitzin
authors.affiliation: 1] Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland [2] Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Lugli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D017920:Antiporters / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000473:pathology* / Q000601:surgery; D012007:Rectum / Q000473:pathology*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D017920:Antiporters; D014408:Biomarkers, Tumor; C489237:SLC4A3 protein, human