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

Abstract

Gestational trophoblastic neoplasms (GTNs) are a rare group of neoplastic diseases composed of choriocarcinomas, placental site trophoblastic tumors (PSTTs) and epithelioid trophoblastic tumors (ETTs). Since these tumors are derivatives of fetal trophoblastic tissue, approximately 50% of GTN cases are expected to originate from a male conceptus and carry a Y-chromosomal complement according to a balanced sex ratio. To investigate this hypothesis, we carried out a comprehensive analysis by genotyping a relatively large sample size of 51 GTN cases using three independent sex chromosome genetic markers; Amelogenin, Protein Kinase and Zinc Finger have X and Y homologues that are distinguishable by their PCR product size. We found that all cases contained the X-chromosomal complement while only five (10%) of 51 tumors harbored the Y-chromosomal complement. Specifically, Y-chromosomal signals were detected in one (5%) of 19 choriocarcinomas, one (7%) of 15 PSTTs and three (18%) of 17 ETTs. The histopathological features of those with a Y-chromosome were similar to those without. Our results demonstrate the presence of a Y-chromosomal complement in GTNs, albeit a low 10% of cases. This shortfall of Y-chromosomal complements in GTNs may reinforce the notion that the majority of GTNs are derived from previous molar gestations.

Gestational Trophoblastic Tumors and Related Tumor-Like Lesions

“…Interestingly, more than 85% of patients with PSTT have had a female antecedent gestation either by history or genetic analysis. Furthermore, PSTTs lack Y chromosomes based on a molecular genetic analysis, suggesting a role of the paternally derived X chromosome in the pathogenesis of PSTT [36,61,77,83,178]. Alternatively, this shortfall of Y-chromosomal complements in PSTTs may reinforce the notion that the majority of PSTTs are derived from previous molar gestations.…”

“…However, the case number in that study is limited to permit from conclusions. The absence of Y chromosome has been demonstrated in the vast majority of choriocarcinomas, indicating that the shortfall of Y chromosomal complements in choriocarcinomas may simply be due to the genetic basis of their precursor lesions, complete hydatidiform moles in which most of cases had the genotype of XX [178].…”

Transformation of a post-cesarean section placental site nodule into a coexisting epithelioid trophoblastic tumor and placental site trophoblastic tumor: a case report

“…Approximately half of ETT cases and 40% of PSN cases are located in the lower uterine segment and/or upper endocervix [3,4,9,11,12]. A recent study showed a lack of a Y-chromosome complement in >80% of cases of ETTs [13]. Analysis of the Y allele in PSNs may be helpful to further clarify the relationship between ETTs and PSNs.…”

Extrauterine Epithelioid Trophoblastic Tumor Arising in the Ovary With Multiple Metastases

“…11 Absence of Y chromosome complement has been observed in the majority of tumors. 15 However, a comparative genomic hybridizataion study showed an undisturbed genome in three cases. 16 Metastasis occurs in 25% of cases and 10% of patients die of disease.…”