Diagnostic utility of microsatellite genotyping for molar pregnancy testing.

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.

[1]  Colin A. Johnson,et al.  Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte. , 2011, American journal of human genetics.

[2]  K. Murphy,et al.  Hydatidiform moles: ancillary techniques to refine diagnosis. , 2011, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[3]  D. Chitayat,et al.  Prospective validation of quantitative fluorescent polymerase chain reaction for rapid detection of common aneuploidies , 2011, Genetics in Medicine.

[4]  J. Lurain.  Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. , 2010, American journal of obstetrics and gynecology.

[5]  P. Hui.  Molecular diagnosis of gestational trophoblastic disease , 2010, Expert review of molecular diagnostics.

[6]  A. Hills,et al.  QF‐PCR as a stand‐alone test for prenatal samples: the first 2 years' experience in the London region , 2010, Prenatal diagnosis.

[7]  P. Hui,et al.  Precise DNA Genotyping Diagnosis of Hydatidiform Mole , 2010, Obstetrics and gynecology.

[8]  A. Clayton,et al.  Comparison of fluorescence in situ hybridization, p57 immunostaining, flow cytometry, and digital image analysis for diagnosing molar and nonmolar products of conception. , 2010, American journal of clinical pathology.

[9]  N. Sebire,et al.  HISTOPATHOLOGICAL DIAGNOSIS OF HYDATIDIFORM MOLE: Contemporary Features and Clinical Implications , 2010, Fetal and pediatric pathology.

[10]  K. Murphy,et al.  Molecular genotyping of hydatidiform moles: analytic validation of a multiplex short tandem repeat assay. , 2009, The Journal of molecular diagnostics : JMD.

[11]  K. Murphy,et al.  Diagnosis and Subclassification of Hydatidiform Moles Using p57 Immunohistochemistry and Molecular Genotyping: Validation and Prospective Analysis in Routine and Consultation Practice Settings With Development of an Algorithmic Approach , 2009, The American journal of surgical pathology.

[12]  L. Dvorakova,et al.  OmniPlex—a new QF‐PCR assay for prenatal diagnosis of common aneuploidies based on evaluation of the heterozygosity of short tandem repeat loci in the Czech population , 2008, Prenatal diagnosis.

[13]  C. Bifulco,et al.  Genotypic Analysis of Hydatidiform Mole: An Accurate and Practical Method of Diagnosis , 2008, The American journal of surgical pathology.

[14]  D. Dawson,et al.  Utility of microsatellite analysis in evaluation of pregnancies with placental mesenchymal dysplasia , 2007, Prenatal diagnosis.

[15]  A. Innes,et al.  Origin and outcome of pregnancies affected by androgenetic/biparental chimerism. , 2007, Human reproduction.

[16]  Michael Wells,et al.  The pathology of gestational trophoblastic disease: recent advances. , 2007, Pathology.

[17]  R. Kuick,et al.  Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans , 2006, Nature Genetics.

[18]  H. Katabuchi,et al.  Interobserver and Intraobserver Variability in the Diagnosis of Hydatidiform Mole , 2005, The American journal of surgical pathology.

[19]  C. Livasy,et al.  Androgenetic/biparental mosaicism causes placental mesenchymal dysplasia , 2005, Journal of Medical Genetics.

[20]  D. Mutch,et al.  Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53. , 2004, Gynecologic oncology.

[21]  Gynecologists.  ACOG Practice Bulletin #53. Diagnosis and treatment of gestational trophoblastic disease. , 2004, Obstetrics and gynecology.

[22]  A. Mitsuhashi,et al.  Placental mesenchymal dysplasia initially diagnosed as partial mole , 2003, Pathology international.

[23]  Yin Shen,et al.  The development of reduced size STR amplicons as tools for analysis of degraded DNA. , 2003, Journal of forensic sciences.

[24]  R. Fisher,et al.  Genomic imprinting in gestational trophoblastic disease--a review. , 2003, Placenta.

[25]  J. Blouin,et al.  Is genetic analysis useful in the routine management of hydatidiform mole? , 2003, Human reproduction.

[26]  N. Sebire,et al.  The maternally transcribed gene p57(KIP2) (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles. , 2002, Human molecular genetics.

[27]  S. Langlois,et al.  Dispermy--origin of diandric triploidy: brief communication. , 2002, Human reproduction.

[28]  D. Genest.  Partial hydatidiform mole: clinicopathological features, differential diagnosis, ploidy and molecular studies, and gold standards for diagnosis. , 2001, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[29]  S. Abbs,et al.  Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis , 2001, The Lancet.

[30]  U. Surti,et al.  Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole. , 2000, American journal of human genetics.

[31]  D. Leonard,et al.  Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole. , 1999, Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology.

[32]  T. Hassold,et al.  Determinants of villous trophoblastic hyperplasia in spontaneous abortions. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[33]  M. Leader,et al.  Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis. , 1993, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[34]  R. Fisher,et al.  A prospective genetic study of complete and partial hydatidiform moles. , 1991, American journal of obstetrics and gynecology.

[35]  Z. Darżynkiewicz,et al.  Analysis of cellular DNA content by flow and laser scanning cytometry. , 2010, Advances in experimental medicine and biology.

[36]  U. Surti,et al.  P57KIP2 immunostaining and molecular cytogenetics: combined approach aids in diagnosis of morphologically challenging cases with molar phenotype and in detecting androgenetic cell lines in mosaic/chimeric conceptions. , 2008, Human pathology.