title: Tumor budding is predictive of lymphatic involvement and lymph node metastases in submucosal invasive colorectal adenocarcinomas and in non-polypoid compared with polypoid growths.
abstract: OBJECTIVE
  Early colorectal carcinomas (submucosal invasive adenocarcinomas) can be classified into polypoid and non-polypoid growth types, the latter progressing more rapidly to advanced malignancy. The aim of this study was to investigate the differences between invasive features of the two types of carcinoma by focusing on tumor budding (isolated single cells or small cell clusters (up to four cells) scattered at invasive tumor margins).
  
  
  METHODS
  The number of foci in the field with the most frequent tumor budding was regarded as "activity". Tumor budding was examined using anti-cytokeratin antibodies in 98 colorectal submucosal invasive adenocarcinomas and compared with the clinicopathological findings. In addition, the relationships between tumor budding and beta-catenin and laminin-5gamma2 expression were analyzed.
  
  
  RESULTS
  Tumor budding activity was significantly higher in non-polypoid growth carcinomas compared with polypoid growth carcinomas (p = 0.0006) and values for left-sided lesions were higher than those for right-sided lesions of the colon (p = 0.0108). Positive links with tumor budding were evident for lymphatic involvement and lymph node metastasis in non-polypoid growth carcinomas, and with laminin-5gamma2 cytoplasmic expression in polypoid growth carcinomas. Multivariate logistic analysis revealed that the activity of tumor budding was an independent risk factor for lymphatic involvement.
  
  
  CONCLUSIONS
  The results indicate that tumor budding makes a greater contribution to progression in non-polypoid than in polypoid growth carcinomas, with possible involvement of lymph node metastasis.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Kitasato, Sagamihara, Kanagawa, Japan. dm03008a@st.kitasato-u.ac.jp
authors.forename: Taishi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuruta
authors.forename: Wataru
authors.initials: W
authors.lastname: Tokuyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Adachi
authors.forename: Masaomi
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Tetuo
authors.initials: T
authors.lastname: Mikami
authors.forename: Katsunori
authors.initials: K
authors.lastname: Saigenji
authors.forename: Isao
authors.initials: I
authors.lastname: Okayasu
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology / Q000556:secondary* / Q000601:surgery; D000368:Aged; D001707:Biopsy, Needle; D003111:Colonic Polyps / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D016015:Logistic Models; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011336:Probability; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D047368:Tumor Burden