BACKGROUND: The anti-cancer mechanism of neo-adjuvant hormonal therapy (NHT) is 
not well understood. Lymphangiogenesis plays an important role in cancer 
progression and is regulated by a complex mechanism that includes vascular 
endothelial growth factor (VEGF) signaling. However, there is little information 
regarding relationship between lymphangiogenesis and androgen deprivation. The 
aim of this study was to clarify changes in lymphangiogenesis and VEGF 
expression induced by androgen deprivation in prostate cancer in vivo and in 
vitro.
METHODS: Patients who had undergone a radical prostatectomy were enrolled in the 
study (NHT, n = 60 and non-NHT, n = 64). Lymph vessels were identified by D2-40 
immunoreactivity and lymph vessel density and lymph vessel area (LVD and LVA, 
respectively) were measured from micrographs. The expression of VEGF-A, -B, -C, 
and -D was evaluated by immunohistochemistry. The prognostic value of LVD and 
LVA for biochemical recurrence was also investigated.
RESULTS: Mean LVD ± SD was higher in the NHT than in the non-NHT group 
(11.3 ± 3.0 vs. 7.1 ± 3.4 per high power field; P < 0.001). LVA was larger in 
the NHT than in the non-NHT group (512.8 ± 174.9 vs. 202.7 ± 72.8 µm2 ; 
P < 0.001). VEGF-A expression was lower whereas VEGF-C and -D levels were higher 
in the NHT than in the non-NHT group. VEGF-B expression in specimens with NHT 
was lower than that in biopsy specimens at diagnosis. These results were 
confirmed by in vitro studies used androgen-sensitive prostate cancer cell line. 
LVA was found to be an independent predictor of biochemical recurrence in 
patients who received NHT.
CONCLUSIONS: Our results demonstrate that NHT stimulates lymphangiogenesis via 
upregulation of VEGF-C and -D, which may increase LVA and affect the outcome of 
prostate cancer patients. This findings were supported by in vitro data of 
prostate cancer cell. Prostate 77:255-262, 2017. © 2016 The Authors. The 
Prostate Published by Wiley Periodicals, Inc.