title: Possible contribution of CD44 variant 6 and nuclear beta-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma.
abstract: BACKGROUND
  In an earlier study, the authors demonstrated that tumor budding was useful for predicting lymph node metastasis in patients with early invasive (T1) colorectal carcinoma. This study was undertaken to clarify the associations between tumor budding, E-cadherin-catenin complex, and CD44 variant 6 abnormalities.
  
  
  METHODS
  In 51 T1 colorectal carcinomas, tumor budding (the number of dedifferentiation units at the invasive margin) on hematoxylin and eosin-stained slides was counted under light microscopy. Immunostaining for E-cadherin, alpha-catenin, beta-catenin, and CD44 variant 6 was performed on formalin fixed, paraffin embedded sections. The associations between locoregional failure (lymph node metastasis or local recurrence) and tumor budding and clinicopathologic parameters and immunoreactivity were examined statistically.
  
  
  RESULTS
  In univariate analysis, tumor budding and nuclear beta-catenin expression were associated significantly with locoregional failure (P = 0.004, 0.01). Multivariate analysis showed that tumor budding alone was associated significantly with locoregional failure (P = 0.02), and the association between nuclear beta-catenin expression and locoregional failure was marginally significant (P = 0.07). Analysis of variance showed that lymphatic invasion alone was associated significantly with tumor budding (P = 0.02), and there was a significant interaction effect for tumor budding between CD44 variant 6 expression and nuclear beta-catenin expression (P = 0.01). There was a significant correlation between expression patterns of these two molecules and locoregional failure (P = 0.01).
  
  
  CONCLUSIONS
  The current results suggest that the up-regulation of CD44 variant 6 through nuclear beta-catenin activation may contribute to the formation of tumor budding, and immunostaining of these two adhesion molecules may be useful in identifying those at high-risk for locoregional failure among patients with T1 colorectal carcinoma.
authors.affiliation: First Department of Surgery, Kyorin University, Tokyo, Japan. masaki@kyorin-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: A
authors.initials: A
authors.lastname: Goto
authors.forename: M
authors.initials: M
authors.lastname: Sugiyama
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
authors.forename: N
authors.initials: N
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Atomi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009364:Neoplasm Recurrence, Local; D012307:Risk Factors; D015534:Trans-Activators; D015854:Up-Regulation; D051176:beta Catenin
chemical_list: C112697:CD44v6 antigen; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D015534:Trans-Activators; D051176:beta Catenin