Genotypic analysis of hydatidiform mole: an accurate and practical method of diagnosis

Molar gestations are defined at the genetic level by their unique parental chromosomal compositions. Their diagnosis, however, currently relies largely on histologic features and on the occasional support of ancillary immunohistochemical and DNA ploidy analyses. We sought to validate DNA genotyping for the routine diagnosis and subtyping of hydatidiform moles (HMs) by analyzing 52 cases of molar pregnancy and their morphologic mimics. DNA was extracted from microdissected chorionic villi and paired maternal endometrial tissue from unstained paraffin sections and analyzed by AmpFlSTR Identifiler PCR Amplification system (Applied Biosystems, Inc). DNA genotyping was informative in all cases with input template DNA amounts ranging from 1.5 to 2.5 ng. Among 38 cases of HMs confirmed by DNA genotyping, there were 26 complete moles with diandric paternal-only genomes (24 homozygous and 2 heterozygous) and 12 partial moles with diandric, monogynic genomes (11 heterozygous and 1 homozygous). All nonmolar cases, including 10 cases of mimics of HM, demonstrated a balanced, biallelic profile of both maternal and paternal origin. Our study demonstrates the applicability of DNA genotyping, the molecular approach for the diagnosis, and subtyping of molar pregnancy, to the daily clinical practice.