Histopathological predictors of regional lymph node metastasis at the invasive front in early colorectal cancer.
OBJECTIVE
In early colorectal cancer (ECC), prediction of lymph node (LN) metastasis is vital for the decision of additional surgical treatment after endoscopic mucosal/submucosal resection. The aim of this study was to determine the relationship between LN metastasis and comprehensive histopathological findings including the cancer microenvironment in ECC.


RESULTS
Using 111 ECC cases, including 36 cases with LN metastasis, histopathological observations and immunohistochemistry for lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, matrix metalloproteinase-7 (MMP-7), CXC chemokine ligand-12 (CXCL12) and angiopoietin-like-4 (ANGPTL4) were conducted. Relationships between LN metastasis and growth pattern, status of muscularis mucosae, depth of cancer invasion, overall histopathological type, histopathological type at the invasive front, tumour budding, neutrophil infiltration in cancer cells (NIC), fibrotic cancer-stroma type, Crohn's-like lymphoid reaction, microscopic abscess formation and lymphatic invasion were determined. In addition, the expression of MMP-7, CXCL12 and ANGPTL4 in cancer cells at the invasive front were also considered in the context of LN metastasis. By multivariate analysis, lymphatic invasion, NIC and MMP-7 expression at the invasive front were independent predictors of LN metastasis.


CONCLUSIONS
LN metastasis is regulated not only by the characteristics of cancer cells but also by microenvironmental factors of lymphatics and neutrophils, especially at the invasive front.
Department of Pathology, Toho University School of Medicine, Tokyo, Japan. yfukasawa@med.toho-u.ac.jp
Yuri
Y
Akishima-Fukasawa
Yukio
Y
Ishikawa
Yoshikiyo
Y
Akasaka
Miwa
M
Uzuki
Naomi
N
Inomata
Tomoko
T
Yokoo
Ryuga
R
Ishii
Reiko
R
Shimokawa
Kiyoshi
K
Mukai
Hideko
H
Kiguchi
Koyu
K
Suzuki
Mieko
M
Fujiwara
Kentaro
K
Ogata
Hitoshi
H
Niino
Hitoshi
H
Sugiura
Akihiro
A
Ichinose
Yoshikazu
Y
Kuroda
Daisuke
D
Kuroda
Toshiharu
T
Ishii
D000368:Aged; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000276:immunology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology
C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D014408:Biomarkers, Tumor; D054377:Chemokine CXCL12; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7