Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas.
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.
Masaki
Tadahiko
T
First Department of Surgery, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
Sugiyama
Masanori
M
Matsuoka
Hiroyoshi
H
Abe
Nobutsugu
N
Izumisato
Yumi
Y
Goto
Akiteru
A
Sakamoto
Atsuhiko
A
Atomi
Yutaka
Y
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
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D051178:alpha Catenin; C004631:3-cyanoalanine; D020783:Matrix Metalloproteinase 7; D000409:Alanine