Myometrial Invasion and Lymph Node Metastasis in Endometrioid Carcinomas: Tumor-associated Macrophages, Microvessel Density, and HIF1A Have a Crucial Role
Myometrial Invasion and Lymph Node Metastasis in Endometrioid Carcinomas: Tumor-associated Macrophages, Microvessel Density, and HIF1A Have a Crucial Role
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DOI：
10.1097/pas.0b013e3181f32168
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发表时间：
2010-11-01
影响因子：
5.6
通讯作者：
Prat, Jaime
中科院分区：
文献类型：
--
作者：
Espinosa, Inigo;Jose Carnicer, Maria;Prat, Jaime
子宫肌层浸润是子宫内膜样癌的独立预后指标，与盆腔和/或腹主动脉旁淋巴结转移风险相关。识别子宫肌层侵犯有时是困难的。事实上，肌侵犯在常规实践中被过度诊断的情况多达25%。最近，已经观察到肿瘤相关巨噬细胞刺激血管生成并促进癌症扩散。本文对64例原发性子宫内膜样癌中50例有肌层浸润和14例无肌层浸润者及20例肌层浸润性肿瘤相应区域淋巴结转移者的肿瘤巨噬细胞（CD 163）、微血管密度（CD 31）和缺氧诱导因子1a亚单位（HIF 1A）进行了检测。子宫内膜样癌伴子宫肌层浸润者的CD 163-肿瘤巨噬细胞数量和微血管密度高于无子宫肌层浸润者（分别为p = 0.000和p = 0.000）。在局限于子宫体的癌（I期）中，HIF 1A的表达与深部肌层浸润（IC期）相关（p = 0.006）。在肌层浸润性和非肌层浸润性肿瘤中，微血管密度与CD 163-巨噬细胞之间均存在显著相关性。另一方面，高级别胶质瘤样癌比低级别肿瘤有更多的巨噬细胞浸润和微血管（p = 0.03和p = 0.07）。原发灶和相应区域淋巴结转移灶中CD 163-巨噬细胞与微血管密度呈正相关。这些发现将增加的微血管增殖与间质巨噬细胞浸润联系起来，并表明由间质巨噬细胞触发的增强的肿瘤血管生成调节类胶质瘤的进展。在原发性和相应的转移性肿瘤中发现的相同的基质微环境表明肿瘤基质反应由肿瘤的内在生物学决定。
Myometrial invasion is an independent prognostic parameter of the endometrioid carcinomas which correlates with the risk of metastasis to pelvic and/or paraaortic lymph nodes. Recognition of myometrial invasion is sometimes difficult. In fact, myoinvasion is overdiagnosed in routine practice in as many as 25% of the cases. Recently, it has been observed that tumor-associated macrophages stimulate angiogenesis and promote cancer dissemination. Tumor macrophages (CD163), microvessel density (CD31), and hypoxia inducible factor 1 a subunit (HIF1A) were investigated in 64 primary endometrioid carcinomas with (50 cases) and without (14 cases) myometrial invasion as well as in the corresponding regional lymph nodes metastases of 20 of the myoinvasive tumors. Endometrioid carcinomas with myometrial invasion showed higher number of CD163-tumor macrophages and greater microvessel density than endometrioid carcinomas without myometrial invasion (p = 0.000 and p = 0.000, respectively). In carcinomas confined to the corpus uteri (stage I), expression of HIF1A was associated with deep myoinvasion (stage IC) (p = 0.006). There was a significant relationship between microvessel density and CD163-macrophages both in the myoinvasive and nonmyoinvasive tumors. On the other hand, high-grade endometrioid carcinomas had more macrophage infiltrates and microvessels than low-grade tumors (p = 0.03 and p = 0.07). Also, there was a positive correlation between CD163-macrophages and microvessel density in the primary tumors and their corresponding regional lymph node metastases. These findings link increased microvessel proliferation to stromal macrophage infiltrate and suggest that enhanced tumor angiogenesis, triggered by stromal macrophages, regulates the progression of endometrioid carcinomas. The identical stroma microenvironment found in the primary and the corresponding metastatic tumor suggests that tumor stroma response is determined by the intrinsic biology of the tumor.