Aromatase expression in stromal cells of endometrioid endometrial cancer correlates with poor survival
Aromatase expression in stromal cells of endometrioid endometrial cancer correlates with poor survival
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DOI：
10.1158/1078-0432.ccr-04-1859
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发表时间：
2005-03-15
影响因子：
11.5
通讯作者：
Inoue, M
中科院分区：
文献类型：
--
作者：
Segawa, T;Shozu, M;Inoue, M
目的和实验设计：为了评估芳香化酶在子宫内膜癌中的预后意义，我们采用免疫组织化学方法对55例子宫内膜癌患者的切片进行了芳香化酶表达的评估，并分析了芳香化酶表达与临床病理参数之间的相关性。芳香化酶的免疫组化染色分别在32例（58%）、20例（36%）和19例（34%）患者的癌上皮细胞、间质细胞和侧腹浸润周围的子宫肌层细胞中呈阳性。原位杂交也检测到芳香化酶mRNA在所有三种类型的细胞。RT-PCR分析显示肿瘤组织中芳香化酶mRNA为2.5 +/- 1.0阿莫尔/μ g总RNA（平均值+/- SE; n = 7）。Western印迹分析检测到预期的芳香化酶蛋白大小为58 kDa的癌组织中比在无癌子宫内膜中更丰富（n = 3）。间质细胞免疫反应阳性率与手术分期及术后生存率呈正相关。生存分析显示，间质细胞的免疫反应性是一个重要的预后因素，独立的组织学分级，肌层浸润，淋巴结转移，但依赖于手术阶段。相比之下，芳香化酶在癌上皮细胞和子宫肌层细胞的免疫反应性与预后无关。结论：据我们所知，这是第一个证据关联瘤内芳香化酶在间质细胞的表达和生存不良的类子宫内膜癌。这种正相关表明芳香化酶的局部表达通过原位雌激素的形成在肿瘤进展中起作用。芳香化酶的原位表达可能为子宫内膜癌的治疗提供一个潜在的靶点。
Purpose and Experimental Design: To assess the prognostic significance of intratumoral aromatase in endometrioid endometrial cancer, sections from 55 patients with endometrial cancer were evaluated for expression of aromatase using immunohistochemistry, and the correlation between aromatase expression and clinicopathologic parameters were analyzed.Results: Immunohistochemical staining for aromatase was positive for 32 (58%), 20 (36%), and 19 (34%) patients in cancer epithelial cells, stromal cells, and myometrial cells around the flank invasion, respectively. In situ hybridization also detected aromatase mRNA in all three types of cells. RT-PCR analysis revealed that aromatase mRNA was 2.5 +/- 1.0 amol/mu g total RNA (mean +/- SE; n = 7) in tumor tissue. Western blot analysis detected the expected aromatase protein size of 58 kDa in cancer tissues more abundantly than in cancer-free endometrium (n = 3). The immunoreactivity in stromal cells correlated positively with advanced surgical stage and poor survival. Survival analysis revealed that the immunoreactivity of stromal cells was a significant prognostic factor, independent of histologic grade, muscular invasion, and lymph node metastasis, but dependent on surgical stage. By contrast, the immunoreactivity of aromatase both in cancer epithelial cells and myometrial cells did not correlate with prognosis.Conclusions: To the best of our knowledge, this is the first evidence associating intratumoral aromatase expression in stromal cells and poor survival in endometrioid endometrial cancer. This positive linkage indicates that local expression of aromatase plays a role in tumor progression through the formation of in situ estrogens. In situ expression of aromatase may offer a potential target for management of endometrial cancers.