title: Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas.
abstract: BACKGROUND
  The clinical utility of relative and absolute grading criteria for submucosal invasion in T1 colorectal carcinomas has been controversial.
  
  
  METHODS
  In 51 T1 colorectal carcinomas, depth of submucosal invasion was graded either according to a modified Haggitt's classification (a relative criterion) or by direct measurement using a micrometer (an absolute criterion), and immunostaining for E-cadherin, alpha-catenin, beta-catenin, matrilysin, and CD44 variant 6 was performed on formalin-fixed, paraffin-embedded sections. The associations between lymph node metastasis or local recurrence (locoregional failure) and tumor budding, and clinicopathologic parameters and immunoreactivity were examined statistically.
  
  
  RESULTS
  By univariate analysis, tumor budding, histology, and the co-expression pattern of nuclear beta-catenin and CD44 variant 6 were significantly associated with locoregional failure. The relative and absolute grading of submucosal invasion were not significantly associated with locoregional failure. Multivariate analysis showed that tumor budding alone was significantly associated with locoregional failure, and the association between the co-expression pattern of nuclear beta-catenin and CD44 variant 6, and locoregional failure was marginally significant ( P = 0.0502). Lymphatic invasion and absolute grading of depth and width of submucosal invasion were significantly associated with tumor budding, and the associations between tumor budding, and histologic differentiation and membranous alpha-catenin expression were marginally significant ( P = 0.06; P= 0.08), whereas, a relative grading of submucosal invasion was not significant ( P = 0.58). Analysis of variance showed that histologic differentiation and lymphatic invasion were independently and significantly associated with tumor budding ( P = 0.005; P < 0.001).
  
  
  CONCLUSIONS
  These results suggest that the grading of submucosal invasion, either relative or absolute, may not be a useful risk factor for lymph node metastasis or local recurrence in T1 colorectal carcinomas.
authors.affiliation: First Department of Surgery, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Masaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Nobutsugu
authors.initials: N
authors.lastname: Abe
authors.forename: Yumi
authors.initials: Y
authors.lastname: Izumisato
authors.forename: Akiteru
authors.initials: A
authors.lastname: Goto
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Atomi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives* / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D051178:alpha Catenin
chemical_list: C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D051178:alpha Catenin; C004631:3-cyanoalanine; D020783:Matrix Metalloproteinase 7; D000409:Alanine