Miyata Yasuyoshi, Mitsunari Kensuke, Asai Akihiro, Takehara Kosuke, Mochizuki Yasushi, Sakai Hideki
Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Prostate. 2015 Jan;75(1):84-91. doi: 10.1002/pros.22894. Epub 2014 Oct 13.
Neoadjuvant hormonal therapy (NHT) is performed to improve the outcome in organ-confined prostate cancer. However, there is little information regarding the relationship between angiogenesis and NHT. The aim of this study was to identify a suitable method to evaluate the angiogenic status of tissue, and to determine the prognostic value of this method for biochemical recurrence in patients who had undergone radical prostatectomy after NHT.
We analyzed 108 formalin-fixed specimens from patients treated by radical prostatectomy. NHT was administered in 48 patients (52.9%) and 60 patients who had a similar Gleason score and pT stage were selected as a non-NHT treated control group. Microvessel density (MVD) was measured using anti-CD31, anti-CD34, and anti-CD105 antibodies. The expressions of vascular endothelial growth factor (VEGF)-A and thrombospondin (TSP)-1 were also evaluated by immunohistochemistry. The prognostic value of CD31-, CD34-, and CD105-MVD for biochemical recurrence was investigated.
The mean/SD of CD105-MVD in the NHT group (13.3/4.7) was significantly (P < 0.001) lower than that in the non-NHT group (125.8/7.3). In the NHT group, CD105-MVD was associated with pT stage and it was positively correlated with VEGF-A expression (r = 0.56, P < 0.001) and negatively correlated with TSP-1 expression (r = 0.42, P = 0.003). CD105-MVD was identified as a significant predictor of biochemical recurrence (BCR) in patients treated with NHT (log rank test, P < 0.001). Although CD31- and CD34-MVD were significantly associated with pT stage or Gleason score in non-NHT group, they were not associated with pathological features and BCR in NHT group.
Our results indicate that CD105-MVD reflects the angiogenic conditions in prostate cancer tissues treated with NHT. CD105-MVD was also identified as a significant and independent predictor of biochemical recurrence in prostate cancer patients who underwent radical prostatectomy with NHT.
新辅助激素治疗(NHT)旨在改善局限性前列腺癌的治疗效果。然而,关于血管生成与NHT之间的关系,目前所知甚少。本研究的目的是确定一种合适的方法来评估组织的血管生成状态,并确定该方法对接受NHT后行根治性前列腺切除术患者生化复发的预后价值。
我们分析了108例接受根治性前列腺切除术患者的福尔马林固定标本。48例患者(52.9%)接受了NHT治疗,并选择60例具有相似Gleason评分和pT分期的患者作为未接受NHT治疗的对照组。使用抗CD31、抗CD34和抗CD105抗体测量微血管密度(MVD)。还通过免疫组织化学评估血管内皮生长因子(VEGF)-A和血小板反应蛋白(TSP)-1的表达。研究了CD31-MVD、CD34-MVD和CD105-MVD对生化复发的预后价值。
NHT组中CD105-MVD的平均值/标准差(13.3/4.7)显著低于未接受NHT治疗的对照组(125.8/7.3)(P < 0.001)。在NHT组中,CD105-MVD与pT分期相关,与VEGF-A表达呈正相关(r = 0.56,P < 0.001),与TSP-1表达呈负相关(r = 0.42,P = 0.003)。CD105-MVD被确定为接受NHT治疗患者生化复发(BCR)的显著预测指标(对数秩检验,P < 0.001)。虽然在未接受NHT治疗的对照组中,CD31-MVD和CD34-MVD与pT分期或Gleason评分显著相关,但在NHT组中,它们与病理特征和BCR无关。
我们的结果表明,CD105-MVD反映了接受NHT治疗的前列腺癌组织中的血管生成情况。CD105-MVD也被确定为接受NHT后行根治性前列腺切除术的前列腺癌患者生化复发的显著且独立的预测指标。