Hui P, Parkash V, Perkins A S, Carcangiu M L
Department of Pathology, Yale University Medical School, New Haven, Connecticut, USA.
Lab Invest. 2000 Jun;80(6):965-72. doi: 10.1038/labinvest.3780099.
Placental site trophoblastic tumor (PSTT) is a neoplastic proliferation of intermediate trophoblasts that invades the myometrium at the placental site after a pregnancy. Less than 100 cases have been reported. Information of the sex assignment of the antecedent gestation is available in 21 cases: 18 of these were female. To explore this interesting phenomenon, we have determined the sex chromosome composition of the tumor tissue preserved in paraffin blocks for five new cases of this condition. The last documented gestational event included a normal vaginal delivery of female infants in three cases, normal vaginal delivery of an infant of unknown sex in one case and a molar gestation in one case. Using the X-linked human androgen receptor (AR) gene as a polymorphic marker, we showed that in all five cases the tumor had a likely XX chromosomal composition; and in four cases it was possible to determine that one of the X chromosomes was of paternal origin. In one case, the paternal X chromosome showed no polymorphism to either maternal X chromosomes. In addition, sensitive semi-nested PCR failed to show a human Y chromosome element in any of the five cases of PSTT. Overall, of 21 cases from the literature and 5 cases of ours, 89% (23 of 26) showed an XX genomic composition in PSTT, either by history or genetic analysis. These results suggest that most PSTT were derived from the antecedent female conceptus and were likely to have possessed a functional paternal X chromosome. Methylation status analysis at the AR locus was performed in the three PSTT in which the paternal X chromosome was identifiable. In two cases, the paternal AR locus was hypomethylated while the corresponding maternal locus was hypermethylated. The methylation status of other loci was not investigated. Collectively, sex chromosome analysis of five cases of PSTT with literature support suggests a unique genetic basis for the development of PSTT that involves the paternal X chromosome. Although largely speculative, an active paternal X chromosome may be of importance in the pathogenesis of PSTT.
胎盘部位滋养细胞肿瘤（PSTT）是中间型滋养细胞的肿瘤性增殖，发生于妊娠后胎盘部位并侵入子宫肌层。报道的病例不足100例。21例中有关于前次妊娠性别信息：其中18例为女性。为探究这一有趣现象，我们测定了5例该疾病石蜡包埋肿瘤组织的性染色体组成。最后记录的妊娠事件包括3例正常阴道分娩女婴、1例正常阴道分娩性别不明的婴儿以及1例葡萄胎妊娠。使用X连锁的人类雄激素受体（AR）基因作为多态性标记，我们发现所有5例肿瘤可能具有XX染色体组成；4例中可以确定其中一条X染色体来自父方。1例中，父方X染色体与母方任何一条X染色体均无多态性。此外，灵敏的半巢式PCR在5例PSTT中均未显示人类Y染色体成分。总体而言，在文献报道的21例和我们的5例中，89%（26例中的23例）通过病史或基因分析显示PSTT具有XX基因组组成。这些结果提示大多数PSTT源自前次女性妊娠产物，且可能具有一条功能性父方X染色体。对3例可识别父方X染色体的PSTT进行了AR基因座的甲基化状态分析。2例中，父方AR基因座低甲基化而相应母方基因座高甲基化。未研究其他基因座的甲基化状态。综合5例PSTT的性染色体分析及文献支持表明，PSTT的发生具有独特的遗传基础，涉及父方X染色体。尽管很大程度上是推测性的，但活跃的父方X染色体可能在PSTT的发病机制中起重要作用。
