{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:55:06Z","timestamp":1777625706087,"version":"3.51.4"},"reference-count":27,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["EBPPG\/2021\/38"],"award-info":[{"award-number":["EBPPG\/2021\/38"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2024,2,28]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>HER2<\/jats:italic>\n                      dual-colour dual-hapten in-situ hybridisation (D-DISH) assay by using the internal chromosome 17 enumeration probe to determine ploidy status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We selected 25 products of conception, consisting of molar and non-molar cases, to validate the\n                      <jats:italic>HER2<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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&lt;0.001). We achieved clear separation of average nuclear signals for diploid and triploid conceptuses, which was statistically significant (p&lt;0.05). Employing our innovative scoring system, known as the \u2018rule of 5\u2019, we established ploidy decision thresholds for all 25 cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our modified\n                      <jats:italic>HER2<\/jats:italic>\n                      D-DISH ploidy assay simplifies the process of ploidy determination and improves the accuracy of morphological diagnosis of molar pregnancy. The\n                      <jats:italic>HER2<\/jats:italic>\n                      D-DISH assay was selected for ploidy analysis due to the widespread availability of in-situ hybridisation in pathology laboratories.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2023-209265","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T13:20:13Z","timestamp":1711804813000},"page":"320-326","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Novel scoring system provides high separation of diploidy and triploidy to aid partial hydatidiform mole diagnosis: an adaption of\n                    <i>HER2<\/i>\n                    D-DISH for ploidy analysis"],"prefix":"10.1136","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7231-8331","authenticated-orcid":false,"given":"Caroline M","family":"Joyce","sequence":"first","affiliation":[{"name":"Pregnancy Loss Research Group, Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland"},{"name":"Bichemistry & Cell Biology, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Dineen","sequence":"additional","affiliation":[{"name":"Pregnancy Loss Research Group, Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland"},{"name":"Department of Pathology, Cork University Hospital, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Deane","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cork University Hospital, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niamh","family":"Conlon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cork University Hospital, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-1711","authenticated-orcid":false,"given":"Paula M","family":"O'Shea","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Diagnostic Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Corcoran","sequence":"additional","affiliation":[{"name":"National Perinatal Epidemiology Centre, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Coulter","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Cork University Maternity Hospital, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-2887","authenticated-orcid":false,"given":"Keelin","family":"O'Donoghue","sequence":"additional","affiliation":[{"name":"Pregnancy Loss Research Group, Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland"},{"name":"Department of Obstetrics & Gynaecology, Cork University Maternity Hospital, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8509-088X","authenticated-orcid":false,"given":"Brendan","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Pregnancy Loss Research Group, Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland"},{"name":"Department of Pathology, Cork University Hospital, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"2025120519362963000_78.5.320.1","doi-asserted-by":"crossref","DOI":"10.1136\/bmjmed-2022-000321","article-title":"Advances in the diagnosis and early management of gestational trophoblastic disease","volume":"1","author":"Joyce","year":"2022","journal-title":"BMJ Med"},{"key":"2025120519362963000_78.5.320.2","doi-asserted-by":"publisher","DOI":"10.3109\/01443615.2013.771159"},{"key":"2025120519362963000_78.5.320.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02432-6"},{"key":"2025120519362963000_78.5.320.4","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20107"},{"key":"2025120519362963000_78.5.320.5","doi-asserted-by":"crossref","unstructured":"McMahon L , Maher GJ , Joyce C , et al . When to consult a geneticist specialising in gestational trophoblastic disease. Gynecol Obstet Invest 2023:26. doi:10.1159\/000531218","DOI":"10.1159\/000531218"},{"key":"2025120519362963000_78.5.320.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.05.002"},{"key":"2025120519362963000_78.5.320.7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-052016-100237"},{"key":"2025120519362963000_78.5.320.8","doi-asserted-by":"crossref","unstructured":"Bartosch C , Nadal A , Braga AC , et al . Practical guidelines of the EOTTD for pathological and genetic diagnosis of hydatidiform moles. 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