Absence of Y chromosome in human placental site trophoblastic tumor

Abstract

Placental site trophoblastic tumor is a neoplasm of extravillous intermediate trophoblast at the implantation site, preceded in the majority of cases by a female gestational event. Our pilot investigation suggested that the development of this tumor might require a paternally derived X chromosome and the absence of a Y chromosome. Twenty cases of placental site trophoblastic tumor were included in this study. Genotyping at 15 polymorphic loci and one sex determination locus was performed by multiplex PCR followed by capillary electrophoresis. X chromosome polymorphisms were determined by PCR amplification of exon 1 of the human androgen receptor gene using primers flanking the polymorphic CAG repeats within this region. Genotyping at 15 polymorphic loci was informative and paternal alleles were present in all tumors, confirming the trophoblastic origin of the tumors. The presence of an X chromosome and the absence of a Y chromosome were observed in all tumors. Among 13 cases in which analysis of the X chromosome polymorphism was informative, all but one demonstrated at least two X alleles and seven cases showed one identifiable paternal X allele. These results confirm a unique pathogenetic mechanism in placental site trophoblastic tumor, involving an exclusion of the Y chromosome from the genome and, therefore, a tumor arising from the trophectoderm of a female conceptus. As epigenetic regulations of imprinting during X chromosome inactivation are of significant biological implications, placental site trophoblastic tumor may provide an important model for studying the sex chromosome biology and the proliferative advantage conferred by the paternal X chromosome.

Lack of a Y-Chromosomal Complement in the Majority of Gestational Trophoblastic Neoplasms

“…Among these five tumors was a PSTT. This finding is in contrast to a previous report demonstrating that none of 13 PSTTs harbored the AMELY [12]. The discrepancy is likely explained by the larger sample size and the additional Y markers employed in this study.…”

“…On the contrary, more than 85% of patients with PSTTs were found by history records or genetic analysis to have had a female antecedent gestation. Moreover, a recent study using the Amelogenin assay demonstrated the presence of a X-chromosome and absence of a Y in a small series of PSTTs [12], raising the possibility that a Y-chromosomal complement may be preferentially deleted in PSTTs. In this paper we describe our findings in a larger number of PSTTs, as well as other types of GTNs including choriocarcinomas and ETTs.…”

Atypical Placental Site Nodule (APSN) and Association With Malignant Gestational Trophoblastic Disease; A Clinicopathologic Study of 21 Cases

“…On the basis of morphologic and immunohistochemical studies, PSN may represent the benign counterpart of ETT and EPSR the counterpart of PSTT. This study was based on results from previous reviews that the unique genetic requirement for neoplastic proliferation in PSTT was the presence of paternal X chromosome and reasoned that if EPSR is a benign counterpart of PSTT or a background condition from which PSTT develops, a similar genetic requirement should exist in EPSR (18,19). Furthermore, lack of a clear biologic link between PSTT and EPSR was demonstrated in a recent study (17).…”

Placental Site Trophoblastic Tumor: A Case Report and Review of the Literature

“…The intermediate trophoblastic cells leave the placenta to restructure the spiral arterioles in order to decrease the blood flow resistance toward the placenta ( 4 , 5 ). PSTTs come from these spiral arterioles ( 6 ).…”