The prognostic value of tumor-associated macrophages in leiomyosarcoma: a single institution study.
The prognostic value of tumor-associated macrophages in leiomyosarcoma: a single institution study.
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DOI：
10.1097/coc.0b013e3181d26d5e
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
West RB
中科院分区：
文献类型：
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作者：
Ganjoo KN;Witten D;Patel M;Espinosa I;La T;Tibshirani R;van de Rijn M;Jacobs C;West RB
大量肿瘤相关巨噬细胞（TAM）与多种实体瘤的不良预后相关。在之前的两项研究中，我们在一项多中心研究中表明，集落刺激因子-1 (CSF1) 由平滑肌肉瘤 (LMS) 分泌，巨噬细胞和 CSF1 相关蛋白的增加是妇科和非妇科 LMS 预后不良的标志。本研究的目的是根据通过 3 个 CSF1 相关蛋白评估的 TAM 数量来评估来自单个机构的 LMS 患者的结果。在斯坦福大学接受治疗且拥有足够存档组织和临床数据的 LMS 患者有资格参加这项回顾性研究。来自图表审查的数据包括肿瘤部位、大小、分级、分期、治疗和上次随访时的疾病状态。通过组织微阵列上的免疫组织化学评估 3 种 CSF1 相关蛋白（CD163、CD16 和组织蛋白酶 L）。 Kaplan-Meier 生存曲线和单变量 Cox 比例风险模型适合评估临床预测因子以及 CSF1 相关蛋白与总生存期的关联。共有 52 名 1983 年至 2007 年诊断的患者接受了评估。单变量 Cox 比例风险模型适合评估等级、大小、阶段和 3 个 CSF1 相关蛋白在预测 OS 中的重要性。在整个患者队列中，分级、大小和分期与生存率没有显着相关，但在妇科 (GYN) LMS 样本中，分级和分期是生存的显着预测因子（分别为 P = 0.038 和 P = 0.0164）。组织蛋白酶 L 增加与 GYN LMS 的较差结果相关（P = 0.049）。 CD16 也有类似的发现（P < 0.0001）。此外，与 CSF1 反应较差的肿瘤相比，CSF1 反应丰富（所有 3 个染色均呈阳性）GYN LMS 的总生存率较差 (P = 0.001)。这些结果在非 GYN LMS 中未见。我们的数据独立证实了 TAM 和 CSF1 相关蛋白在 LMS 中的预后意义。对于高度表达这些标志物的 LMS 患者亚群，可以考虑采取更积极或更有针对性的治疗。
High numbers of tumor-associated macrophages (TAMs) have been associated with poor outcome in several solid tumors. In 2 previous studies, we showed that colony stimulating factor-1 (CSF1) is secreted by leiomyosarcoma (LMS) and that the increase in macrophages and CSF1 associated proteins are markers for poor prognosis in both gynecologic and nongynecologic LMS in a multicentered study. The purpose of this study is to evaluate the outcome of patients with LMS from a single institution according to the number of TAMs evaluated through 3 CSF1 associated proteins. Patients with LMS treated at Stanford University with adequate archived tissue and clinical data were eligible for this retrospective study. Data from chart reviews included tumor site, size, grade, stage, treatment, and disease status at the time of last follow-up. The 3 CSF1 associated proteins (CD163, CD16, and cathepsin L) were evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier survival curves and univariate Cox proportional hazards models were fit to assess the association of clinical predictors as well as CSF1 associated proteins with overall survival. A total of 52 patients diagnosed from 1983 to 2007 were evaluated. Univariate Cox proportional hazards models were fit to assess the significance of grade, size, stage, and the 3 CSF1 associated proteins in predicting OS. Grade, size, and stage were not significantly associated with survival in the full patient cohort, but grade and stage were significant predictors of survival in the gynecologic (GYN) LMS samples (P = 0.038 and P = 0.0164, respectively). Increased cathepsin L was associated with a worse outcome in GYN LMS (P = 0.049). Similar findings were seen with CD16 (P < 0.0001). In addition, CSF1 response enriched (all 3 stains positive) GYN LMS had a poor overall survival when compared with CSF1 response poor tumors (P = 0.001). These results were not seen in non-GYN LMS. Our data form an independent confirmation of the prognostic significance of TAMs and the CSF1 associated proteins in LMS. More aggressive or targeted therapies could be considered in the subset of LMS patients that highly express these markers.