Multiplex Short Tandem Repeat (STR) Genotyping of Complete Hydatidiform Moles: Analysis of Zygosity and Presence of Invasive Gestational Trophoblastic Disease at Presentation
Niloofar Nasseri-Nik, Cheryl DeScipio, Kathleen M Murphy, Russell Vang, Brigitte M Ronnett. The Johns Hopkins Medical institutions, Baltimore, MD
Background: The vast majority of complete hydatidiform moles (CHM) are androgenetic diploid, with most (>80%) arising from fertilization of an egg lacking maternal DNA by a single sperm that duplicates (monospermic/homozygous 46,XX) and a small subset arising via fertilization by 2 sperm (dispermic/heterozygous 46,XY or 46,XX). It remains controversial whether dispermic/heterozygous CHMs have a significantly greater risk of persistent gestational trophoblastic disease (GTD). Analysis of zygosity of CHMs with and without invasive GTD at presentation has not been specifically addressed.
Design: In a series of 390 products of conception specimens analyzed by p57 immunohistochemistry and STR genotyping for diagnosis and subclassification of hydatidiform moles, 125 CHMs were diagnosed. Of these, 69 were genotyped (including all with invasive disease). Zygosity was compared between those with and without invasive GTD at presentation.
Results: Of the 69 genotyped CHMs, 7 (10%) were invasive CHMs at presentation (in hysterectomy specimens); 2 of these were accompanied by choriocarcinoma in the uterus, 1 with pulmonary nodules consistent with metastatic GTD. 10 of 69 (14%) CHMs were dispermic (all XY) and 59 (86%) were monospermic (XX). 5 of 59 (8.5%) monospermic CHMs and 2 of 10 (20%) dispermic CHMs were invasive at presentation (p=0.27). The 2 invasive CHMs accompanied by pathologically documented choriocarcinoma were monospermic.
Conclusions: Dispermic XY CHMs, which represent only ∼15% of CHMs, have a greater risk of being invasive at presentation but this difference did not reach statistical significance. However, the 2 examples of invasive CHMs associated with choriocarcinoma were monospermic XX, indicating that this form is not without risk of significant GTD. Follow-up analysis is required to assess the risk of persistent GTD in these 2 genetic types of CHMs.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 161, Wednesday Morning