Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth
Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth
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DOI：
10.1016/j.ajog.2015.02.016
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发表时间：
2015-08-01
影响因子：
9.8
通讯作者：
Miyagi, Etsuko
中科院分区：
文献类型：
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作者：
Asano, Ryoko;Asai-Sato, Mikiko;Miyagi, Etsuko
目的：肌瘤性红细胞增多症是一种罕见的子宫肌瘤并发症，由肿瘤细胞产生的促红细胞生成素（EPO）引起。我们评估了EPO在平滑肌瘤中的表达，并探讨了EPO对肿瘤生长的影响。研究设计：组织样本收集了114例子宫平滑肌瘤患者进行肌瘤切除术或子宫切除术在横滨市立大学医院。从17例患者中，还收集了相应的正常子宫肌层。通过实时逆转录-聚合酶链反应分析所有样本的EPO信使RNA（mRNA）表达。酶联免疫吸附试验测定EPO蛋白表达。使用患者病历回顾性分析EPO表达与临床病理特征的关系。血管密度和成熟度采用苏木精-伊红染色和CD 34免疫组化进行评估。结果：114例平滑肌瘤中108例（95%）检测到EPO mRNA表达。子宫肌瘤中EPO mRNA的平均表达高于相应的正常子宫肌层（3836 +/- 4122 vs 1455 +/- 2141; Wilcoxon秩检验P = 0.025）。在不同的样本中，子宫肌瘤中EPO mRNA的表达差异很大，从检测不到的水平到高于正常子宫肌层EPO mRNA平均水平的18倍不等。EPO蛋白的产生与mRNA的表达同时进行。斯皮尔曼等级相关系数（rho = 0.294; P = 0.001）显示肌瘤大小与EPO mRNA表达呈正相关，提示EPO参与肌瘤生长。血管成熟度也显着增加，在EPO生产平滑肌瘤（高血管成熟度在高与低EPO组：67%比20%; P = 0.013 Fisher精确检验）。结论：本报告表明，EPO是在大多数传统平滑肌瘤和支持的模型，其中EPO加速肿瘤生长，可能是通过诱导血管成熟。我们的研究提示了一种可能的机制，通过这种机制，一些子宫平滑肌瘤达到大的尺寸，并了解EPO在这些肿瘤中的表达模式可能有助于平滑肌瘤患者的管理。
OBJECTIVE: Myomatous erythrocytosis syndrome is a rare complication of uterine leiomyoma caused by erythropoietin (EPO) that is produced by tumor cells. We assessed the EPO expression in leiomyomas and investigated the effects of EPO on the tumor growth.STUDY DESIGN: Tissue samples were collected from 114 patients with uterine leiomyomas who underwent myomectomy or hysterectomy in Yokohama City University Hospital. From 17 patients, the corresponding normal myometrium was also collected. All samples were analyzed for EPO messenger RNA (mRNA) expression by real-time reverse transcription-polymerase chain reaction. EPO protein expression was determined by an enzyme-linked immunosorbent assay. The relationships between EPO expression and clinicopathological features were retrospectively analyzed using the patients' charts. Blood vessel density and maturity were assessed using hematoxylin-eosin staining and CD34 immunohistochemistry.RESULTS: EPO mRNA expression was detected in 108 of 114, or 95%, of the leiomyomas. The mean EPO mRNA expression in the leiomyoma was higher than the corresponding normal myometrium (3836 +/- 4122 vs 1455 +/- 2141; P = .025 by Wilcoxon rank test). The EPO mRNA expression in the leiomyomas varied extensively among samples, ranging from undetectable levels to 18-fold above the mean EPO mRNA of normal myometrium. EPO protein production was observed concomitant with mRNA expression. A positive correlation of leiomyoma size and EPO mRNA expression was shown by Spearman rank correlation coefficient (rho = 0.294; P = .001), suggesting the involvement of EPO in leiomyoma growth. The blood vessel maturity was also significantly increased in EPO-producing leiomyomas (high vessel maturity in high vs low EPO group: 67% vs 20%; P = .013 by Fisher exact test).CONCLUSION: This report demonstrates that EPO is produced in most of conventional leiomyomas and supports a model in which EPO accelerates tumor growth, possibly by inducing vessel maturity. Our study suggests one possible mechanism by which some uterine leiomyomas reach a large size, and the understanding of EPO expression patterns in these tumors may be useful for management of the patients with leiomyomas.