Document Detail

Diagnostic reproducibility of hydatidiform moles: ancillary techniques (p57 immunohistochemistry and molecular genotyping) improve morphologic diagnosis for both recently trained and experienced gynecologic pathologists.
MedLine Citation:
PMID:  22992698     Owner:  NLM     Status:  MEDLINE    
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.
Mamta Gupta; Russell Vang; Anna V Yemelyanova; Robert J Kurman; Fanghong Rose Li; Emily C Maambo; Kathleen M Murphy; Cheryl DeScipio; Carol B Thompson; Brigitte M Ronnett
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The American journal of surgical pathology     Volume:  36     ISSN:  1532-0979     ISO Abbreviation:  Am. J. Surg. Pathol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-01-21     Revised Date:  2013-08-23    
Medline Journal Info:
Nlm Unique ID:  7707904     Medline TA:  Am J Surg Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1747-60     Citation Subset:  IM    
Departments of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA.
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MeSH Terms
Clinical Competence
Clinical Laboratory Techniques* / standards
Cyclin-Dependent Kinase Inhibitor p57 / analysis*,  genetics*
Hydatidiform Mole / chemistry,  classification,  diagnosis*,  genetics,  pathology
Immunohistochemistry* / standards
Linear Models
Molecular Diagnostic Techniques* / standards
Observer Variation
Odds Ratio
Polymerase Chain Reaction
Predictive Value of Tests
Prospective Studies
Reproducibility of Results
Sensitivity and Specificity
Tumor Markers, Biological / analysis*,  genetics*
Uterine Neoplasms / chemistry,  classification,  diagnosis*,  genetics,  pathology
Grant Support
Reg. No./Substance:
0/CDKN1C protein, human; 0/Cyclin-Dependent Kinase Inhibitor p57; 0/Tumor Markers, Biological

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