RT Journal Article SR Electronic T1 Novel scoring system provides high separation of diploidy and triploidy to aid partial hydatidiform mole diagnosis: an adaption of HER2 D-DISH for ploidy analysis JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 320 OP 326 DO 10.1136/jcp-2023-209265 VO 78 IS 5 A1 Joyce, Caroline M A1 Dineen, Susan A1 Deane, Julie A1 Conlon, Niamh A1 O'Shea, Paula M A1 Corcoran, Paul A1 Coulter, John A1 O'Donoghue, Keelin A1 Fitzgerald, Brendan YR 2025 UL http://jcp.bmj.com/content/78/5/320.abstract AB Aims Diagnosis of hydatidiform mole or molar pregnancy based on morphology alone can be challenging, particularly in early gestation, necessitating the use of ancillary techniques for accurate diagnosis. We sought to adapt the VENTANA HER2 dual-colour dual-hapten in-situ hybridisation (D-DISH) assay by using the internal chromosome 17 enumeration probe to determine ploidy status.Methods We selected 25 products of conception, consisting of molar and non-molar cases, to validate the HER2 D-DISH assay. These cases had prior morphological assessment by a perinatal pathologist and ploidy analysis using molecular cytogenetics. Three independent observers, blinded to the original histopathological and genetic diagnosis, scored 10 representative areas on each slide. Interobserver variability was assessed by comparing the total scores of each observer using analysis of variance (ANOVA) and the kappa statistic.Results Our ploidy scoring system accurately determined the correct number of diploid and triploid conceptuses, demonstrating complete concordance with pre-existing ploidy status and the initial diagnosis. Interobserver agreement between three independent scorers was robust: ANOVA (p=0.36) and kappa statistic (0.812, p<0.001). We achieved clear separation of average nuclear signals for diploid and triploid conceptuses, which was statistically significant (p<0.05). Employing our innovative scoring system, known as the ‘rule of 5’, we established ploidy decision thresholds for all 25 cases.Conclusions Our modified HER2 D-DISH ploidy assay simplifies the process of ploidy determination and improves the accuracy of morphological diagnosis of molar pregnancy. The HER2 D-DISH assay was selected for ploidy analysis due to the widespread availability of in-situ hybridisation in pathology laboratories.All data relevant to the study are included in the article or uploaded as supplemental information.