Vascular Endothelial Growth Factor-C and -D Expression Correlates With Lymph Node Micrometastasis in pN0 Early Gastric Cancer

Background and Objectives: Vascular endothelial growth factors (VEGF)-C and -D play an important role in lymphangiogenesis, and the expressions of these factors are related to lymphatic invasion and lymph node metastasis in various malignant neoplasms. The present study investigates the expression of VEGF-C and -D in early gastric cancer and analyzes its relationship to lymph node micrometastasis determined by reverse transcription-polymerase chain reaction (RT-PCR). Methods: We examined 1,828 lymph nodes obtained from 80 patients with node-negative early gastric cancer. All dissected lymph nodes were examined by RT-PCR for CEA mRNA in addition to hematoxylin-eosin staining. The resected primary specimens were immunostained using anti-VEGF-C and -D polyclonal antibodies. Results: The incidence of lymph node micrometastasis determined by RT-PCR was 23.8% (19/80). The high expression of VEGF-C and -D was found in 27.5% (22/80) and in 21.3% (17/80). respectively. The expression of VEGF-C and -D was closely related to lymph node micrometastasis (P = 0.0390 and 0.0213, respectively). Conclusions: We demonstrated a close relationship between micrometastasis and VEGF-C and -D expression of the primary tumor. Thus, levels of VEGF-C and -D expression might be useful for predicting micrometastasis in patients with early gastric cancer.