Diagnostic Utility of Microsatellite Genotyping for Molar Pregnancy Testing

Abstract

Context.—Molecular genotyping by analysis of DNA microsatellites, also known as short tandem repeats (STRs), is an established method for diagnosing and classifying hydatidiform mole. Distinction of both complete hydatidiform mole and partial hydatidiform mole from nonmolar specimens is relevant for clinical management owing to differences in risk for persistent gestational trophoblastic disease. Objective.—To determine the technical performance of microsatellite genotyping by using a commercially available multiplex assay, and to describe the application of additional methods to confirm other genetic abnormalities detected by the genotyping assay. Design.—Microsatellite genotyping data on 102 cases referred for molar pregnancy testing are presented. A separate panel of mini STR markers, flow cytometry, fluorescence in situ hybridization, and p57 immunohistochemistry were used to characterize cases with other incidental genetic abnormalities. Results.—Forty-eight cases were classified as hydatidiform mole (31, complete hydatidiform mole; 17, partial hydatidiform mole). Genotyping also revealed 11 cases of suspected trisomy and 1 case of androgenetic/biparental mosaicism. Trisomy for selected chromosomes (13, 16, 18, and 21) was confirmed in all cases by using a panel of mini STR markers. Conclusions.—This series illustrates the utility of microsatellite genotyping as a stand-alone method for accurate classification of hydatidiform mole. Other genetic abnormalities may be detected by genotyping; confirmation of the suspected abnormality requires additional testing.

Placental Molar Disease

“…Secondly, suboptimal pathologist marking or technical microdissection of conceptus and maternal tissues can also lead to maternal contamination. The lower proportion of noninformative genotype testing noted in other studies (3,20) may reflect more strict case inclusion criteria; in our pilot study genotyping attempts were undertaken even in the most challenging cases. In addition, the higher proportion of noninformative tests in this study may be attributable to our stringent criterion for informative testing that requires 2 markers per chromosome.…”

“…A report from another placental molar referral service has yielded similar findings. In this report of 102 cases referred for suspected molar disease 54 (or about 50%) were subsequently classified as HA (20). In the absence of a PMD Service it is probable that most or many of these HA cases would have been labeled as ''HM'' or ''suspicious for HM,'' and women would have received unnecessary biochemical and clinical follow-up (1).…”

“…This criterion has been adopted to meet standards of good practice in the detection of aneuploidy. Noninformative genotyping does represent a potential barrier to the adoption of genotyping, but can be minimized by undertaking meticulous methods and corrective steps for microdissection and construction of paraffin block (20).…”

“…A diagnostic algorithm incorporating immunohistochemistry and genotyping has been offered (10)(11)(12). However, there has been only limited application of genotyping into routine clinical practice (8,20). Several factors may be responsible for the limited use of genotyping, but foremost among these may be its lack of availability in many pathology laboratories thus necessitating external referral (20).…”

“…However, there has been only limited application of genotyping into routine clinical practice (8,20). Several factors may be responsible for the limited use of genotyping, but foremost among these may be its lack of availability in many pathology laboratories thus necessitating external referral (20). Consequently, the implementation of an advance in diagnostics has been slow, and reliance still placed upon imprecise and inaccurate morphologic techniques.…”