- 36 例生殖细胞来源滋养细胞肿瘤:双相绒癌 16、单相绒癌 4、囊性滋养细胞肿瘤(CTT)9、未分类滋养细胞肿瘤(UTT)6、上皮样滋养细胞肿瘤(ETT)1;多见于化疗后。
- 非绒癌型(CTT/UTT/ETT)miR-371a-3p 显著低于双相绒癌(P=0.0002),但仍高于畸胎瘤(P=0.0129)。
- 甲基化聚类:CTT、UTT、ETT 与畸胎瘤聚为一类,生殖细胞来源绒癌与妊娠滋养细胞肿瘤聚为一类——提示前者是“分化型”滋养细胞表型。
收录范围:PubMed 英文摘要及中文翻译(abstract-only);AJSP(Wolters Kluwer)为订阅制在线优先文章,无开放全文,未采集全文图表。
摘要
生殖细胞来源的少见滋养细胞肿瘤——上皮样滋养细胞肿瘤(ETT)、未分类滋养细胞肿瘤(UTT)、囊性滋养细胞肿瘤(CTT)和单相绒毛膜癌(MChorio)——较为罕见,且大多见于化疗后。它们与其他生殖细胞肿瘤类型及妊娠性肿瘤的关系仍不明确。我们利用 microRNA-371~373 水平和 DNA 甲基化谱,将非绒癌型生殖细胞来源滋养细胞肿瘤与妊娠滋养细胞肿瘤及青春期后型畸胎瘤进行比较。
共纳入 36 例生殖细胞来源滋养细胞肿瘤(双相绒毛膜癌 16 例、MChorio 4 例、CTT 9 例、UTT 6 例、ETT 1 例)。采用 RT-qPCR 检测生殖细胞来源滋养细胞肿瘤的 microRNA-371~373 水平,并与非滋养细胞性睾丸生殖细胞肿瘤及妊娠滋养细胞肿瘤(n=50)比较。对生殖细胞来源滋养细胞肿瘤采用 EPIC 芯片进行 DNA 甲基化谱分析,并与青春期后型畸胎瘤及妊娠滋养细胞肿瘤(n=28)比较。
非绒癌型生殖细胞来源滋养细胞肿瘤的 miR-371a-3p 水平显著低于生殖细胞来源双相绒毛膜癌(P=0.0002)。与畸胎瘤相比,分化中的滋养细胞肿瘤保留较高的 miR-371a-3p 水平(P=0.0129)。基于差异甲基化最显著探针的分析显示,生殖细胞来源的 CTT、UTT 和 ETT 与畸胎瘤聚类,而生殖细胞来源的绒毛膜癌则与妊娠滋养细胞肿瘤聚类。DNA 甲基化模式显示由绒毛膜癌向畸胎瘤样谱逐渐分化的趋势。
我们的结果提示,生殖细胞来源的 ETT、UTT 和 CTT 代表与畸胎瘤相似的“分化型”滋养细胞肿瘤表型,而生殖细胞来源的绒毛膜癌则与妊娠滋养细胞肿瘤相似。
- 36 germ cell-derived trophoblastic tumours: biphasic choriocarcinoma 16, monophasic choriocarcinoma 4, CTT 9, UTT 6, ETT 1; mostly postchemotherapy.
- Nonchoriocarcinoma trophoblastic tumours had lower miR-371a-3p than biphasic choriocarcinoma (P=0.0002) but higher than teratoma (P=0.0129).
- By methylation, CTT, UTT and ETT clustered with teratoma, whereas germ cell-derived choriocarcinomas clustered with gestational trophoblastic tumours.
Scope: PubMed abstract only. AJSP (Wolters Kluwer) online-ahead-of-print article without open full text; figures and tables were not collected.
Abstract
Unusual trophoblastic tumors of germ cell origin-epithelioid trophoblastic tumor (ETT), unclassified trophoblastic tumor (UTT), cystic trophoblastic tumor (CTT), and monophasic choriocarcinoma (MChorio)-are rare and mostly encountered postchemotherapy. Their relationship to other germ cell tumor types and gestational tumors remains uncertain. We used microRNA‑371~373 levels and DNA methylation profiling to compare nonchoriocarcinoma germ cell-derived trophoblastic tumors to gestational trophoblastic neoplasms and postpubertal-type teratoma.
A total of 36 trophoblastic tumors of germ cell origin were included (biphasic choriocarcinoma [n=16], MChorio [n=4], CTT [n=9], UTT [n=6], and ETT [n=1]). MicroRNA‑371~373 levels were assessed by RT‑qPCR on germ cell-derived trophoblastic tumors and compared with nontrophoblastic testicular germ cell tumors and gestational trophoblastic tumors (n=50). DNA methylation profiling was performed using EPIC array on germ cell-derived trophoblastic tumors and compared with postpubertal-type teratomas and gestational trophoblastic tumors (n=28).
Nonchoriocarcinoma trophoblastic tumors of germ cell origin showed significantly lower miR‑371a‑3p levels than germ cell-derived biphasic choriocarcinomas (P=0.0002). Compared with teratoma, differentiating trophoblastic tumors retained higher miR‑371a‑3p levels (P=0.0129). Analyses performed using the top differentially methylated probes revealed that CTT, UTT, and ETT of germ cell origin clustered with teratoma, while choriocarcinomas of germ cell origin clustered with gestational trophoblastic tumors. DNA methylation patterns showed increasing differentiation from choriocarcinoma toward teratoma-like profiles.
Our results suggest that germ-cell-derived ETT, UTT, and CTT represent "differentiated" trophoblastic tumor phenotypes with similarities to teratoma, whereas germ-cell-derived choriocarcinomas resemble gestational trophoblastic tumors.