VEGF-C expression in breast cancer: clinical importance.

It is well known that angiogenesis and lymphangiogenesis play important roles in tumor occurrence and progression. The vascular endothelial growth factor (VEGF) family is the most important family of proteins involved in angiogenesis, and VEGF-C is the most important molecule in lymphangiogenesis. Lymphangiogenesis plays an important role in lymphovascular invasion, metastasis to regional lymph nodes, and distant organ metastasis. In this study, the rate of VEGF-C was investigated in 217 patients with breast cancer. VEGF-C was evaluated by immunohistochemistry and its expression was compared with that of well-known prognostic indicators, such as tumor stage and grade, axillary lymph node involvement, estrogen and progesterone receptor status, c-erb-B2 expression, and extent of lymphovascular invasion. The patient population included 8 men, in addition to women before (n=108), during (n=9), and after (n=92) menopause. Patients had been diagnosed with invasive ductal (n=181) or invasive lobular (n=22) carcinoma, mixed (n=8) or medullary (n=1) carcinoma, or ductal carcinoma in situ (n=5). Tumors ranged from stage 0 to IV and grade I to III and the distribution of estrogen-positive (n=100) and estrogen-negative (n=110) receptor tumors was almost equal. The number of patients with c-erbB2 tumors ranged from 21 to 49 for each tumor stage, and the number of patients with VEGF-C-negative tumors ranged from 28 to 59 for each tumor stage. No important association between VEGF-C expression and other prognostic indicators was found. However, this may be a result of the lack of standardization among the methods used to determine VEGF-C expression. Also, the lymphangiogenic effect may not be overt because of the variety of VEGFR-3 variants, which included nonfunctional variants. To determine the relationship among angiogenesis, lymphangiogenesis, and prognosis, more standardized methods to demonstrate the angiogenesis, and prospective studies to cover a larger, more homogenous patient population are needed.