title: Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57 immunohistochemistry and molecular genotyping) improve morphologic diagnosis for both recently trained and experienced gynecologic pathologists.
abstract: Distinction of hydatidiform moles from nonmolar specimens (NMs) and subclassification of hydatidiform moles as complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) are important for clinical practice and investigational studies; however, diagnosis based solely on morphology is affected by interobserver variability. Molecular genotyping can distinguish these entities by discerning androgenetic diploidy, diandric triploidy, and biparental diploidy to diagnose CHMs, PHMs, and NMs, respectively. Eighty genotyped cases (27 CHMs, 27 PHMs, 26 NMs) were selected from a series of 200 potentially molar specimens previously diagnosed using p57 immunohistochemistry and genotyping. Cases were classified by 6 pathologists (3 faculty level gynecologic pathologists and 3 fellows) on the basis of morphology, masked to p57 immunostaining and genotyping results, into 1 of 3 categories (CHM, PHM, or NM) during 2 diagnostic rounds; a third round incorporating p57 immunostaining results was also conducted. Consensus diagnoses (those rendered by 2 of 3 pathologists in each group) were also determined. Performance of experienced gynecologic pathologists versus fellow pathologists was compared, using genotyping results as the gold standard. Correct classification of CHMs ranged from 59% to 100%; there were no statistically significant differences in performance of faculty versus fellows in any round (P-values of 0.13, 0.67, and 0.54 for rounds 1 to 3, respectively). Correct classification of PHMs ranged from 26% to 93%, with statistically significantly better performance of faculty versus fellows in each round (P-values of 0.04, <0.01, and <0.01 for rounds 1 to 3, respectively). Correct classification of NMs ranged from 31% to 92%, with statistically significantly better performance of faculty only in round 2 (P-values of 1.0, <0.01, and 0.61 for rounds 1 to 3, respectively). Correct classification of all cases combined ranged from 51% to 75% by morphology and 70% to 80% with p57, with statistically significantly better performance of faculty only in round 2 (P-values of 0.69, <0.01, and 0.15 for rounds 1 to 3, respectively). p57 immunostaining significantly improved recognition of CHMs (P<0.01) and had high reproducibility (κ=0.93 to 0.96) but had no impact on distinction of PHMs and NMs. Genotyping provides a definitive diagnosis for the ∼25% to 50% of cases that are misclassified by morphology, especially those that are also unresolved by p57 immunostaining.
authors.affiliation: Departments of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA.
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
authors.forename: Russell
authors.initials: R
authors.lastname: Vang
authors.forename: Anna V
authors.initials: AV
authors.lastname: Yemelyanova
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
authors.forename: Fanghong Rose
authors.initials: FR
authors.lastname: Li
authors.forename: Emily C
authors.initials: EC
authors.lastname: Maambo
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Cheryl
authors.initials: C
authors.lastname: DeScipio
authors.forename: Carol B
authors.initials: CB
authors.lastname: Thompson
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Ronnett
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002983:Clinical Competence; D019411:Clinical Laboratory Techniques / Q000592:standards; D032921:Consensus; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000032:analysis* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006828:Hydatidiform Mole / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry / Q000592:standards; D016014:Linear Models; D025202:Molecular Diagnostic Techniques / Q000592:standards; D015588:Observer Variation; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011247:Pregnancy; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014594:Uterine Neoplasms / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57