Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole2

Ka, Bell; Deerlin, Van; Addya, Kathakaly; Cv, Clevenger; Dg, Leonard

doi:10.1016/s1084-8592(99)80045-9

Cited by 52 publications

(21 citation statements)

References 32 publications

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“…However, previous studies have demonstrated that diagnosis of hydatidiform moles based on morphology alone, even by experienced pathologists with specialized training, is subject to interobserver variability and therefore suboptimal diagnostic reproducibility. [9][10][11][12][13][14][15] A number of studies have demonstrated the value of ancillary techniques, including immunohistochemical analysis of cyclin-dependent kinase inhibitor 1C (CDKN1C/p57/Kip2, the protein product of the CDKN1C imprinted gene located at chromosome 11p15.5; referred to henceforth as p57) expression [16][17][18][19][20][21][22][23][24][25][26][27] and molecular genotyping via PCR amplification of short tandem repeat loci, 23,25,[28][29][30][31] for improving the diagnosis of hydatidiform moles. Genotyping is particularly valuable because it allows for specific distinction of complete hydatidiform moles, partial hydatidiform moles, and nonmolar specimens from one another due to their unique genetics.…”

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confidence: 99%

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

et al. 2014

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Immunohistochemical analysis of cyclin-dependent kinase inhibitor 1C (CDKN1C, p57, Kip2) expression and molecular genotyping accurately classify hydatidiform moles into complete and partial types and distinguish these from non-molar specimens. Characteristics of a prospective series of all potentially molar specimens encountered in a large gynecologic pathology practice are summarized. Initially, all specimens were subjected to both analyses; this was later modified to triage cases for genotyping based on p57 results: p57-negative cases diagnosed as complete hydatidiform moles without genotyping; all p57-positive cases genotyped. Of the 678 cases, 645 were definitively classified as complete hydatidiform mole (201), partial hydatidiform mole (158), non-molar (272), and androgenetic/biparental mosaic (14); 33 were unsatisfactory, complex, or problematic. Of the 201 complete hydatidiform moles, 104 were p57-negative androgenetic and an additional 95 were p57-negative (no genotyping), 1 was p57-positive (retained maternal chromosome 11) androgenetic, and 1 was p57-non-reactive androgenetic; 90 (85%) of the 106 genotyped complete hydatidiform moles were monospermic and 16 were dispermic. Of the 158 partial hydatidiform moles, 155 were diandric triploid, with 154 p57-positive, 1 p57-negative (loss of maternal chromosome 11), and 1 p57-non-reactive; 3 were triandric tetraploid, with 2 p57-positive and 1 p57-negative (loss of maternal chromosome 11). Of 155 diandric triploid partial hydatidiform moles, 153 (99%) were dispermic and 2 were monospermic. Of the 272 non-molar specimens, 259 were p57-positive biparental diploid, 5 were p57-positive digynic triploid, 2 were p57-negative biparental diploid (no morphological features of biparental hydatidiform mole), and 6 were p57-non-reactive biparental diploid. Of the 14 androgenetic/biparental mosaics with discordant p57 expression, 6 were uniformly mosaic and 8 had a p57-negative androgenetic molar component. p57 expression is highly correlated with genotyping, serves as a reliable marker for diagnosis of complete hydatidiform moles, and identifies androgenetic cell lines in mosaic conceptions. Cases with aberrant and discordant p57 expression can be correctly classified by genotyping.

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Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

et al. 2014

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“…21 Several studies have demonstrated the proof of concept and utility of STR genotyping for distinction of CHMs, PHMs, and NMs. 16,17,19 However, none of these reports provides a technical validation that includes specific details regarding how STR data were interpreted, criteria for accepting or rejecting data, and sources of technical and interpretive problems. In the current report we have used a set of retrospective, morphologically typical cases of HMs and NMs to develop an algorithm for the interpretation of STR genotyping data, including specific quantitative criteria for interpretation of results.…”

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Molecular Genotyping of Hydatidiform Moles

Murphy

McConnell

Hafez

et al. 2009

The Journal of Molecular Diagnostics

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Distinction of hydatidiform moles from non-molar (NM) specimens , as well as their subclassification as complete (CHM) versus partial hydatidiform moles (PHM), is important for clinical management and accurate risk assessment for persistent gestational trophoblastic disease. Because diagnosis of hydatidiform moles based solely on morphology suffers from poor interobserver reproducibility , a variety of ancillary techniques have been developed to improve diagnosis. Immunohistochemical assessment of the paternally imprinted , maternally expressed p57 gene can identify CHMs (androgenetic diploidy) by their lack of p57 expression , but cannot distinguish PHMs (diandric monogynic triploidy) from NMs (biparental diploidy). Short tandem repeat genotyping can identify the parental source of polymorphic alleles and thus discern androgenetic diploidy , diandric triploidy, and biparental diploidy , which allows for specific diagnosis of CHMs , PHMs , and NMs , respectively. In this study , a retrospectively collected set of morphologically typical CHMs (n ‫؍‬ 8) , PHMs (n ‫؍‬ 10), and NMs (n ‫؍‬ 12) was subjected to an analytic validation study of both short tandem repeat genotyping and p57 immunohistochemistry. Several technical and biological problems resulted in data that were difficult to interpret. To avoid these pitfalls, we have developed an algorithm with quantitative guidelines for the interpretation of short tandem repeat genotyping data. (J Mol

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“…By identifying the genotypes of maternal and villous tissues at multiple STR loci and determining the parental source of polymorphic alleles and their ratios in villous tissues, STR assays can classify molar pregnancies. Several recent studies 26,27,31,[33][34][35] have shown that STR genotyping can accurately distinguish between androgenetic diploid CHMs and biparental diploid NMAs and between triploid diandric monogynic PHMs and triploid digynic monoandric nonmolar POCs. STR genotyping can be performed on paraffinembedded tissue.…”

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Diagnosis of Hydatidiform Moles by Polymorphic Deletion Probe Fluorescence in Situ Hybridization

Chiang

Fazlollahi

Nguyen

et al. 2011

The Journal of Molecular Diagnostics

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Because products of conception often contain maternal and villous tissues, the determination of maternal and villous genotypes based on genetic polymorphisms can help discern maternal and paternal chromosomal contribution and aid in the diagnosis of hydatidiform moles. Polymorphic deletion probe (PDP) fluorescence in situ hybridization (FISH) probes based on copy number variants are highly polymorphic and allow in situ determination of genetic identity. By using three informative PDPs on chromosomes 2p, 4q, and 8p, we compared maternal with villous genotypes and determined the ploidy of villous tissue. PDP FISH was performed on 13 complete moles, 13 partial moles, 13 nonmolar abortions, and an equivocal hydropic abortion. PDP FISH permitted definitive diagnosis of complete moles in five of 13 cases for which maternal and villous genotypes were mutually exclusive. A complete mole was highly suspected when all three PDP loci showed homozygous villous genotypes. The diagnosis of a complete mole by PDP FISH yielded a theoretical test sensitivity of 87.5%, specificity of 91.8%, an observed test sensitivity of 100%, and specificity of 92.3%. Triploidy was observed in all partial moles, in which diandric triploidy was confirmed in six cases. In the equivocal hydropic abortion, PDP FISH combined with p57 immunofluorescence revealed placental androgenetic/biparental mosaicism. PDP FISH can be used in clinical practice and research studies to subclassify hydatidiform moles and evaluate unusual products of conception. ( J Mol Diagn 2011, 13:406 -415;

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Molecular genetic testing from paraffin-embedded tissue distinguishes nonmolar hydropic abortion from hydatidiform mole2

Cited by 52 publications

References 32 publications

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping

Molecular Genotyping of Hydatidiform Moles

Diagnosis of Hydatidiform Moles by Polymorphic Deletion Probe Fluorescence in Situ Hybridization

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