title: Tumour budding correlates with local recurrence of rectal cancer.
abstract: OBJECTIVE
  Predictive tools for local recurrence (LR) of rectal cancer are needed. This study assessed the predictive value of tumour budding detected by MNF-116 and laminin-5 γ2 chain (Ln-5 γ2).
  
  
  METHODS
  In a case-control study, the surgical specimens of 48 patients with LR after from primary resection of rectal carcinoma and 82 control patients matched for gender and preoperative radiation from a population of 1180 patients operated with total mesorectal excision were studied. The presence of budding was examined using immunohistochemistry with Ln-5 γ2 and pan-cytokeratin staining with MNF-116.
  
  
  RESULTS
  Tumour budding counts ranged from 0 to 106 buds (mean 43, median 38) for all patients. Significantly more tumours with more than 35 buds were seen in the LR than in the control group (67 vs 44%; P = 0.02). The spread of budding was also more extensive in the LR than in the control group (63 vs 49%, P = 0.03). In a multivariate analysis with tumour, node, metastasis stage, MNF-116-stained budding was an independent predictor of local failure (P = 0.02). The budding frequency was higher in irradiated tumours in comparison with tumours that had not received irradiation (mean 53 vs 38, P = 0.03). For Ln-5 γ2, more tumours with ≥ 10 buds were seen in the group with LR than among the control patients, but this difference was not statistically significant (73 vs 57%; P = 0.09). No additive value was found in the multivariate logistic regression model when Ln-5 γ2-stained budding frequency was added to MNF-116 and tumour, node, metastasis stage. The agreement between budding frequency determined by MNF-116 and Ln-5 γ2 was moderate, with a κ-coefficient of 0.34 (0.16-0.51).
  
  
  CONCLUSIONS
  Tumour budding determined by MNF-116 staining may serve as a predictive marker for LR in rectal cancer.
authors.affiliation: Department of Surgery, Ersta Hospital, Stockholm, Sweden. erik.syk@erstadiakoni.se
authors.forename: E
authors.initials: E
authors.lastname: Syk
authors.forename: C
authors.initials: C
authors.lastname: Lenander
authors.forename: P J
authors.initials: PJ
authors.lastname: Nilsson
authors.forename: C A
authors.initials: CA
authors.lastname: Rubio
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism* / Q000528:radiation effects; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling
chemical_list: D014408:Biomarkers, Tumor; C400567:LAMC2 protein, human; D007797:Laminin; C526516:cytokeratin MNF116, human; D007633:Keratins