肿瘤相关巨噬细胞与子宫内膜样腺癌中孕激素受体缺失相关。

Tumor-associated macrophages correlate with progesterone receptor loss in endometrial endometrioid adenocarcinoma.

作者信息

Jiang Xue-feng, Tang Qiong-lan, Li Hai-gang, Shen Xi-ming, Luo Xin, Wang Xiao-yu, Lin Zhong-qiu

机构信息

Department of Obstetrics and Gynecology, First Affiliated Hospital of Jinan University, Guangzhou, China.

出版信息

J Obstet Gynaecol Res. 2013 Apr;39(4):855-63. doi: 10.1111/j.1447-0756.2012.02036.x. Epub 2012 Oct 29.

DOI:10.1111/j.1447-0756.2012.02036.x

PMID:23106983

Abstract

AIM

It has been well established that tumor-associated macrophages (TAMs) play a tumor promoting role in endometrial endometrioid adenocarcinoma (EEC). But the association with TAMs and sex hormone receptor expression, and progression of precancerous endometrial lesions in EEC has been little reported.

MATERIAL AND METHODS

We used immunohistochemistry to examine the expression of CD68, CD34, vascular endothelial growth factor (VEGF), estrogen receptor (ER) and progesterone receptor (PR) in 95 cases of EEC, as well as 35 cases of endometrial hyperplasia (including 15 atypical hyperplasia, 10 complex hyperplasia and 10 simple hyperplasia). We also correlated TAMs count with various clinicopathological factors, sex hormone receptor, and prognostic value in patients with EEC.

RESULTS

We identified that TAMs count increased linearly with disease progression (mean count per case at × 200 magnification: simple hyperplasia, 6.30; complex hyperplasia, 11.20; atypical hyperplasia, 29.40; EEC 55.81, respectively; P < 0.001), that microvascular density (MVD) also increased accordingly (27.50, 30.20, 50.13 and 59.94, respectively; P < 0.001). The expression of progesterone receptor, not of estrogen receptor, significantly decreased with disease progression (P < 0.05). Moreover, histopathologic grades, International Federation of Gynecology and Obstetrics (FIGO) stage (2009), depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, and expression of PR and VEGF were associated with TAMs count (P = 0.0001, P = 0.004, P = 0.0001, P = 0.04, P = 0.0001, P = 0.0001, P = 0.0001, respectively). Progesterone receptor expression was also associated with histopathologic grades, lymphovascular space invasion, VEGF and high TAMs (P = 0.035, P = 0.022, P = 0.014, P = 0.001, respectively). The estimated 5-year survival rate of patients with low TAMs was significantly higher than those with high TAMs (96.4% vs 69.8%, P = 0.002).

CONCLUSION

TAMs are potentially related to PR loss and progression of precancerous endometrial lesions in EEC.

摘要

目的

肿瘤相关巨噬细胞（TAMs）在子宫内膜样腺癌（EEC）中发挥促肿瘤作用，这一点已得到充分证实。但TAMs与性激素受体表达以及EEC中癌前子宫内膜病变进展之间的关联鲜有报道。

材料与方法

我们采用免疫组织化学方法检测了95例EEC以及35例子宫内膜增生（包括15例不典型增生、10例复杂性增生和1例单纯性增生）中CD68、CD34、血管内皮生长因子（VEGF）、雌激素受体（ER）和孕激素受体（PR）的表达。我们还将EEC患者的TAMs计数与各种临床病理因素、性激素受体及预后价值进行了关联分析。

结果

我们发现TAMs计数随疾病进展呈线性增加（×200放大倍数下每例平均计数：单纯性增生为6.30；复杂性增生为11.20；不典型增生为29.40；EEC为55.81；P<0.001），微血管密度（MVD）也相应增加（分别为27.50、30.20、50.13和59.94；P<0.001）。孕激素受体而非雌激素受体的表达随疾病进展显著降低（P<0.05）。此外，组织病理学分级、国际妇产科联盟（FIGO）分期（2009年）、肌层浸润深度、盆腔淋巴结转移、淋巴管间隙浸润以及PR和VEGF的表达均与TAMs计数相关（P分别为0.0001、0.004、0.0001、0.04、0.0001、0.0001、0.0001）。孕激素受体表达还与组织病理学分级、淋巴管间隙浸润、VEGF以及高TAMs相关（P分别为0.035、0.022、0.014、0.001）。TAMs低表达患者的估计5年生存率显著高于TAMs高表达患者（96.4%对69.8%，P=0.002）。