Yuri Prahara, Shigemura Katsumi, Kitagawa Koichi, Hadibrata Exsa, Risan Muhammad, Zulfiqqar Andy, Soeroharjo Indrawarman, Hendri Ahmad Z, Danarto Raden, Ishii Aya, Yamasaki Saya, Yan Yongmin, Heriyanto Didik S, Fujisawa Masato
Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Jl. Kesehatan No. 1, Yogyakarta, 55281, Indonesia.
Division of Urology, Department of Organ Therapeutics, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.
Prostate Int. 2020 Jun;8(2):62-69. doi: 10.1016/j.prnil.2019.12.001. Epub 2020 Feb 10.
Tumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival.
Fifty-four specimens were collected and stained with CD 68 antibody to investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after PCa diagnosis.
The median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated with increasing tumor angiogenesis ( < 0.001, r = 0.61), and the response to ADT was significantly better in patients with fewer TAMs (<28) than in patients with higher TAMs (>28) ( = 0.003). TAM infiltration was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for response to ADT in PCa ( < 0.0001). An increased infiltration of TAM [hazards ratio (HR) = 4.47; 95% confidence interval (CI): 1.97-10.15], MVD (HR = 2.66; 95% CI: 1.27-5.61), metastatic status (HR = 2.29; 95% CI: 0.14-0.60), and prostate volume (HR = 2.19; 95% CI: 1.27-3.12) significantly correlated with shorter survival in PCa patients by univariate analysis ( < 0.05). Multivariate analyses revealed that TAM and metastatic status significantly correlated with poor overall survival.
TAM infiltration is associated with response to ADT and increased tumor angiogenesis in PCa. GS, ADT type, and MVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.
肿瘤相关巨噬细胞（TAM）和微血管密度（MVD）在前列腺癌（PCa）的肿瘤进展中起着至关重要的作用。在本研究中，我们评估了TAM、肿瘤血管生成浸润与PCa中雄激素剥夺疗法（ADT）反应之间的关联，以评估TAM浸润作为PCa生存的预测因素。
收集54份标本，用CD 68抗体染色以研究肿瘤中的TAM浸润。用血管性血友病因子染色以评估癌灶周围的MVD。我们评估了患者年龄、术前血清前列腺特异性抗原、病理Gleason评分（GS）、TAM浸润、MVD与PCa诊断后5年ADT反应之间的关联。
在28（6 - 76）/高倍视野（x400）中观察到TAM的中位数。TAM增加与肿瘤血管生成增加相关（<0.001，r = 0.61），TAM较少（<28）的患者对ADT的反应明显优于TAM较高（>28）的患者（= 0.003）。血清前列腺特异性抗原较高、GS较高和有转移的患者中TAM浸润明显更高。多因素分析表明，GS、ADT类型和MVD数量是PCa中ADT反应的重要预后因素（<0.0001）。单因素分析显示，TAM浸润增加[风险比（HR）= 4.47；95%置信区间（CI）：1.97 - 10.15]、MVD（HR = 2.66；95% CI：1.27 - 5.61）、转移状态（HR = 2.29；95% CI：0.14 - 0.60）和前列腺体积（HR = 2.19；95% CI：1.27 - 3.12）与PCa患者较短的生存期显著相关（<0.05）。多因素分析显示，TAM和转移状态与总体生存率差显著相关。
TAM浸润与PCa中ADT反应及肿瘤血管生成增加相关。PCa标本中的GS、ADT类型和MVD是ADT反应不佳的有用预测因素。TAM增加和转移状态阳性是PCa患者生存期较差的预后因素。
