Vascular Endothelial Growth Factor–C (VEGF-C) Expression in Normal Human Tissues

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Abstract
Objective: To characterize vascular endothelial growth factor-C (VEGF-C) protein expression in normal human tissues by immunohistochemistry (IHC). VEGF-C is a growth factor for lymphatic endothelial cells. VEGF-C mRNA and protein are expressed in a variety of cancerous tissues, but the localization of VEGF-C protein in many normal human tissues has not been clearly demonstrated to date. We therefore performed an immunohistochemical survey of the distribution of intracellular VEGF-C protein in a range of normal human tissue types. Methods: Five µm sections were cut from archived human tissues. Sections were dewaxed, rehydrated, and subjected to microwave pretreatment. They were incubated with VEGF-C antibody before detection with biotinylated secondary antibody using 'Elite' avidin-biotin enzyme complex and diaminobenzidine substrate. The primary antibody recognized the C-terminus of the VEGF-C propeptide that is cleaved before secretion and hence only cellular protein was detected. Negative controls used the same concentration of normal goat IgG. Results: Staining manifested as small punctate cytoplasmic granules. Strong expression was observed in large intestine epithelium, and mammary duct epithelium, skeletal and cardiac muscle, thyroid, ovary, and the prostate. Weaker expression was also detected in the hepatocytes close to the terminal hepatic venules of the liver, vascular smooth muscle, and placenta. No expression was consistently detected in spleen or thymus. Conclusions: Intracellular VEGF-C protein is widely expressed in many normal human adult tissues. Its expression in cancer is not therefore per se indicative of a prolymphangiogenic change. To demonstrate the latter, a quantitative change in expression level is required.

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