Lymphagenesis in gastrointestinal tumors is not well described. To clarify its presence and regulation, we assessed the microlymphatic count (MLC) in colorectal cancer patients. Lymphatic vessels were evaluated by enzyme-histochemistry for 5'-nucleotidase (5'-NA). Since vascular endothelial growth factor (VEGF)-C is reportedly associated with lymphagenesis, the expression of VEGF-C protein was immunohistochemically assessed by the catalyzed signal amplification (CSA) method. MLC of peritumoral lesions was significantly higher than that of non-cancer and intratumoral lesions (p<0.01); it increased where VEGF-C was highly expressed (p<0.01) and increased with the depth of invasion in peritumoral lesions. These results indicate significant findings at peritumoral lesion: that lymphagenesis may be elicited by tumor spread; that VEGF-C expression is associated with lymphagenesis and is a potent factor stimulating lymphagenesis.

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