{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:38:08Z","timestamp":1786527488111,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      DICER1 is a microRNA biogenesis enzyme that, when mutated, results in a rewiring of the transcriptome. Germline pathogenic variants (PVs) in\n                      <jats:italic>DICER1<\/jats:italic>\n                      result in DICER1\u2010related tumour predisposition (DRTP) characterized by 30 or more different, generally rare, paediatric or adolescent\u2010onset tumours. One of these, pituitary blastoma, upregulates let\u20107 targets such as HMGA2, with overexpression at the protein level. In this study, we determined if HMGA2 upregulation involves other tumours characteristic of DRTP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Seventy\u2010eight lesions with confirmed\n                      <jats:italic>DICER1<\/jats:italic>\n                      PVs were studied including CNS spindle cell sarcoma, Sertoli\u2013Leydig cell tumour of the ovary, pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma of ovary or cervix, thyroid follicular nodular disease and seven other more rare diagnoses. Using immunohistochemistry and scoring any degree of nuclear staining for HMGA2 as positive, we found that all lesion types were positive. This was seen in all samples within each category (except one case), but in only 50% of thyroid lesions. Normal control tissues were uniformly negative.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The widespread expression in DICER1\u2010related lesions, benign or malignant, suggests that HMGA2 expression is an early event in the pathogenesis. As HMGA2 is implicated in epithelial to mesenchymal transition, over\u2010expression of HMGA2 in DICER1\u2010related lesions could be driving this transition. Excluding thyroid lesions, immunostaining for HMGA2 shows 98% positivity in DICER1\u2010related lesions, in DRTP or in tumours with somatic mutations. HMGA2 immunostaining could serve as a useful exclusion test; patients with lesions suspected of being DICER1\u2010related, but negative for HMGA2, would be unlikely to benefit from germline\n                      <jats:italic>DICER1<\/jats:italic>\n                      testing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70255","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:09:46Z","timestamp":1786525786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HMGA2<\/scp>\n                    is a highly sensitive marker for\n                    <scp>DICER1<\/scp>\n                    \u2010related tumours"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-5566","authenticated-orcid":false,"given":"Paul S.","family":"Thorner","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9484-7937","authenticated-orcid":false,"given":"Anne\u2010Laure","family":"Chong","sequence":"additional","affiliation":[{"name":"Cancer Axis, Lady Davis Institute Jewish General Hospital  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-1737","authenticated-orcid":false,"given":"Naciba","family":"Benlimane","sequence":"additional","affiliation":[{"name":"Research Pathology Facility, Lady Davis Institute Jewish General Hospital  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2261-0902","authenticated-orcid":false,"given":"Lili","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-7604","authenticated-orcid":false,"given":"Marc R.","family":"Fabian","sequence":"additional","affiliation":[{"name":"Cancer Axis, Lady Davis Institute Jewish General Hospital  Montreal Quebec Canada"},{"name":"Gerald Bronfman Department of Oncology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-4651","authenticated-orcid":false,"given":"William D.","family":"Foulkes","sequence":"additional","affiliation":[{"name":"Cancer Axis, Lady Davis Institute Jewish General Hospital  Montreal Quebec Canada"},{"name":"Gerald Bronfman Department of Oncology McGill University  Montreal Quebec Canada"},{"name":"Division of Medical Genetics, Department of Specialized Medicine, Jewish General Hospital McGill University  Montreal Quebec Canada"},{"name":"Department of Human Genetics McGill University  Montreal Quebec Canada"},{"name":"Cancer Research Program Research Institute of the McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/path.4135","article-title":"Cancer\u2010associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse\u2010strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage","volume":"229","author":"Anglesio MS","year":"2012","journal-title":"J. Pathol."},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1002\/humu.23877","article-title":"Ten years of DICER1\u00a0mutations: Provenance, distribution, and associated phenotypes","volume":"40","author":"Kock L","year":"2019","journal-title":"Hum. Mutat."},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1056\/NEJMoa1102903","article-title":"Recurrent somatic DICER1\u00a0mutations in nonepithelial ovarian cancers","volume":"366","author":"Heravi\u2010Moussavi A","year":"2012","journal-title":"N. Engl. J. 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Cancer Prev."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70255","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70255","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:09:50Z","timestamp":1786525790000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":27,"alternative-id":["10.1111\/his.70255"],"URL":"https:\/\/doi.org\/10.1111\/his.70255","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"assertion":[{"value":"2026-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"his.70255"}}