Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients' survival and responses to androgen deprivation therapies in Indonesian patients cohort
Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients' survival and responses to androgen deprivation therapies in Indonesian patients cohort
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DOI：
10.1016/j.prnil.2019.12.001
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发表时间：
2020-06-01
影响因子：
3
通讯作者：
Fujisawa, Masato
中科院分区：
文献类型：
--
作者：
Yuri, Prahara;Shigemura, Katsumi;Fujisawa, Masato
背景：肿瘤相关巨噬细胞（TAM）和微血管密度（MVD）在前列腺癌（PCa）的肿瘤进展中起重要作用。在这项研究中，我们评估了TAM、滤过与肿瘤血管生成和对前列腺癌雄激素剥夺治疗（ADT）的反应之间的相关性，以评估滤过中的TAM作为前列腺癌生存的预测因素。材料与方法：收集54例肿瘤标本，用CD 68抗体染色，观察TAM在肿瘤中的浸润情况。VonWillebrand因子染色检测癌灶周围微血管密度。我们评估了患者年龄、术前血清前列腺特异性抗原、病理Gleason总和（GS）、滤过中的TAM、MVD和PCa诊断后5年ADT反应之间的关系。结果：在28（6-76）/高倍视野（x400）中观察到中位TAM。TAM增加与肿瘤血管生成增加相关（P < 0.001，r = 0.61），TAM较少的患者（28例）对ADT的反应明显优于TAM较高的患者（28例）（P = 0.003）。血清前列腺特异性抗原高、GS高、有转移的患者，其滤过液中TAM明显增高。多因素分析显示GS、ADT类型和MVD数是影响ADT疗效的重要预后因素（P < 0.0001）。TAM滤过率增加[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）和前列腺体积单因素分析显示，PCa患者的生存率与高血压相关（HR = 2.19; 95% CI：1.27-3.12），与低血压相关（P < 0.05）。多因素分析显示TAM和转移状态与总生存率低显著相关。结论：滤过中的TAM与ADT的反应和PCa中肿瘤血管生成的增加相关。PCa标本中的GS、ADT类型和MVD是ADT疗效差的有用预测因素。增加TAM和阳性转移状态是PCa患者生存率较差的预后因素。(c)2020年亚洲太平洋前列腺学会。Elsevier B. V.的出版服务。这是一篇开放获取的文章
Background: 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 in fi ltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM in fi ltration as a predictive factor for PCa survival. Materials and methods: Fifty-four specimens were collected and stained with CD 68 antibody to investigated TAM in fi ltration 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 -speci fi c antigen, pathologic Gleason sum (GS), TAM in fi ltration, MVD, and the response to ADT for 5 years after PCa diagnosis. Results: The median TAM was observed in 28 (6-76)/high power fi eld (x400). Increasing TAM correlated with increasing tumor angiogenesis ( P < 0.001, r = 0.61), and the response to ADT was signi fi cantly better in patients with fewer TAMs ( 28) than in patients with higher TAMs ( 28) ( P = 0.003). TAM in fi ltration was signi fi cantly higher in those with higher serum prostate -speci fi c antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were signi fi cant prognostic factors for response to ADT in PCa ( P < 0.0001). An increased in fi ltration of TAM [hazards ratio (HR) = 4.47; 95% con fi dence 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) signi fi cantly correlated with shorter survival in PCa patients by univariate analysis ( P < 0.05). Multivariate analyses revealed that TAM and metastatic status signi fi cantly correlated with poor overall survival. Conclusions: TAM in fi ltration 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. (c) 2020 Asian Paci fi c Prostate Society. Publishing services by Elsevier B.V. This is an open access article