title: Markedly elevated cell turnover is characteristic of small, deeply invasive carcinomas of the colorectum.
abstract: BACKGROUND
  Small, deeply invasive carcinomas invading the muscularis propria or deeper and measuring < or = 2 cm in greatest dimension (S-ADV) are rare in comparison with their larger counterparts (NS-ADV), and their clinicopathologic features are obscure.
  
  
  METHODS
  S-ADV and NS-ADV cases as well as cases of submucosal carcinoma (SM-CA) were comparatively assessed for: 1) clinicopathologic findings; 2) Ki-67, mitotic, and apoptotic indices; 3) cathepsin G, p53, and bcl-2 immunoreactivities; and 4) c-Ki-ras mutations.
  
  
  RESULTS
  S-ADV and SM-CA, which both are significantly smaller than NS-ADV, did not differ in size, but the frequency of moderately and poorly differentiated carcinoma elements at the leading edges was observed to be higher than in the central cores only in S-ADV, as was tumor "budding" of small clusters of undifferentiated carcinoma cells. The frequency of severe lymphatic involvement in S-ADV was as high as in NS-ADV, and significantly greater than in SM-CA. The Ki-67, mitotic, and apoptotic indices for S-ADV were significantly increased compared with those for NS-ADV and/or SM-CA. Expression of cathepsin G in S-ADV tumor and stromal cells was significantly decreased compared with NS-ADV and/or SM-CA cases. No significant differences in the expression of either p53 or bcl-2 or the incidence of c-Ki-ras mutations were observed among the three groups.
  
  
  CONCLUSIONS
  S-ADV can be considered a distinct type of deeply invasive carcinoma, presenting with poor tumor differentiation at the leading edge, and with increased tumor cell proliferation despite its small size.
authors: Department of Pathology, School of Medicine, Kitasato University, Kanagawa, Japan.
authors: H
authors: H
authors: Takahashi
authors: H
authors: H
authors: Mitomi
authors: M
authors: M
authors: Igarashi
authors: T
authors: T
authors: Katsumata
authors: I
authors: I
authors: Okayasu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002402:Cathepsin D / Q000032:analysis; D056649:Cathepsin G; D002403:Cathepsins / Q000032:analysis; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000473:pathology; D003110:Colonic Neoplasms / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012004:Rectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D012697:Serine Endopeptidases; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D002402:Cathepsin D