• early colorectal cancer;
  • lymphatic invasion;
  • budding;
  • lymphatic endothelial hyaluronan receptor 1 antibody;
  • cell adhesion molecules



Early colorectal cancer (ECC) is curable by endoscopic local resection; however, 10% of patients with ECC exhibit lymph node (LN) metastasis. In the current study, accurate predictors for LN metastasis in patients with ECC were examined by using immunohistochemistry with the lymphatic endothelial hyaluronan receptor 1 (LYVE-1) antibody to discriminate between lymphatics and blood vessels.


Colorectal tissue specimens obtained from 71 patients with ECC, including 28 patients with regional LN metastasis, were immunostained with antibodies against LYVE-1, β-catenin, claudin-3, claudin-4, and cytokeratin. The significance of the histopathologic variables for LN metastasis in ECC was investigated on the basis of specific histopathologic parameters.


Lymphatic invasion confirmed by LYVE-1 immunohistochemistry was observed mainly in the submucosal area around the primary tumor and rarely was observed in the tumor. Expression patterns of β-catenin, claudin-3, and claudin-4 in cancer cells at the invasive front were irrelevant to LN status. Tumor size, depth of invasion, histologic tumor type, budding formation, and lymphatic invasion were statistically significant to LN status in univariate analysis; however, only 2 factors—lymphatic invasion and budding formation at the invasive front—were independent predictors of LN metastasis in ECC.


LYVE-1 immunohistochemistry appeared to be a useful method for detecting lymphatics invaded by cancer cells, and detailed examination of the submucosa around the tumor may be important for predicting LN metastasis. When lymphatic invasion and budding formation are observed histopathologically in patients with ECC, additional therapy, such as adjuvant chemotherapy or a curative resection of the regional LN, may be required. Cancer 2008. © 2008 American Cancer Society.