Diagnosis and Subclassification of Hydatidiform Moles Utilizing p57 Immunohistochemistry and Molecular Genotyping: Validation and Prospective Analysis with Development of an Algorithmic Approach
TG McConnell, K Murphy, M Hafez, RS Vang, BM Ronnett. Johns Hopkins Medical Institutions, Baltimore, MD
Background: Distinction of hydatidiform moles (HM) from non-molar specimens and subclassification of HMs as complete (CHM), partial (PHM), or early CHM (eCHM) are important for clinical practice and investigational studies but diagnosis based solely on morphology suffers from poor interobserver reproducibility. Recent studies have demonstrated the utility of p57 immunostaining and molecular genotyping for improving diagnosis of HMs.
Design: A validation study of p57 immunostaining and genotyping with the AmpFISTR Profiler kit was performed on 24 archival specimens (7 CHM, 8 PHM, 9 non-molar). Prospective analysis of 42 consecutive cases (83% consultation) for which there was any consideration of a diagnosis of HM was conducted. After satisfactory experience with prospective cases, a modified diagnostic approach was adopted, with p57 immunostaining used with morphology to triage selection of cases for genotyping.
Results: Final diagnoses for the prospective cases were 24 CHMs (including 7 eCHMs), 7 PHMs, and 11 non-molar. P57 immunostaining was negative in all CHMs, with the exception of 1 molecularly confirmed CHM with diffuse p57 expression, and positive in all PHMs and non-molar specimens, with the exception of 3 molecularly confirmed PHMs with an equivocal extent of p57 expression. Molecular genotyping of 51 cases (24 validation, 27 prospective) yielded data consistent with p57 results in the 47 cases with unequivocal p57 expression patterns and was used to establish diagnoses for the 4 with aberrant or equivocal p57 results. All 17 genotyped CHMs demonstrated androgenetic diploidy, including the CHM with retained p57 expression; this case also demonstrated trisomy 11 (retained maternal allele accounting for aberrant p57 expression). The remaining 14 CHMs were diagnosed by morphology and negative p57 results alone. All 15 PHMs demonstrated diandric triploidy. All genotyped non-molar specimens demonstrated biparental diploidy.
Conclusions: This study validates p57 immunostaining as a prospectively applicable triage assay for diagnosis of CHMs based on morphology and a negative p57 result. Molecular genotyping is validated as a method to confirm a diagnosis of CHM by demonstrating androgenetic diploidy and to resolve p57-positive cases into diandric triploid PHMs, biparental diploid non-molar specimens, and the rare CHM with aberrant p57 expression.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 159, Tuesday Afternoon