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

Abstract

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.

Accuracy of p57KIP2 compared with genotyping to diagnose complete hydatidiform mole: a systematic review and meta‐analysis

“…Seven publications met the eligibility criteria and were included in the systematic review 1, 8, 12, 13, 20, 21, 22. The basic characteristics of the included studies were study sample size ranging from 16 to 80 women with ages ranging from 13 to 55 years old (Supporting Information Appendix S3).…”

“…For Gupta et al,22 the p57 KIP2 immunostaining significantly improved recognition of CHMs and had high reproducibility; additionally, the 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 KIP2 immunostaining. Finally, Banet et al12 found that p57 KIP2 expression is highly correlated with genotyping, serving as a reliable marker for the CHM diagnosis, and identifying androgenetic cell lines in mosaic conceptions.…”

“…Three of the studies refer to the same population 12, 21. and only two of these studies13, 21 provided quantitative data, we used only the most recent data published21 to avoid duplication.…”

“…Differentiating a molar pregnancy from nonmolar specimens (NMS) and the classification of HM as CHM (including early CHM), PHM, or hydropic miscarriage are important for both clinical practice and investigational studies because of the risk of development of gestational trophoblastic neoplasia (GTN), including choriocarcinoma, which is significantly higher after a pregnancy affected by CHM (15–27%) or PHM (0.5–5%) then with any other pregnancy 10, 11, 12, 13…”

Placental Molar Disease

“…There are 3 cytogenetic origins for HM. Diandric diploid conceptuses result in a complete hydatidiform mole (CM); and are most often caused by fertilization by a single X-bearing sperm of an empty (nullisomic) ovum with subsequent endoreduplication of the haploid sperm DNA content manifesting as exclusively paternal homozygous genome (complete uniparental disomy) (2,3). Partial hydatidiform mole (PM) typically results from a diandric triploid conceptus with 2 paternal haploid and 1 gynic haploid genome.…”