{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:15:24Z","timestamp":1792023324720,"version":"4.4.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Parrainage Tumeurs gyn\u00e9cologiques of Gustave Roussy."},{"name":"Canc\u00e9rop\u00f4le Lyon Auvergne-Rh\u00f4ne-Alpes (CLARA)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Therapeutic options are limited for patients with high-grade ovarian carcinoma (HGOC) progressing after poly(adenosine diphosphate-ribose) polymerase-inhibitor (PARPi). WEE1\/CDK2-inhibitors efficacy is under investigation in HGOC harbouring\n                      <jats:italic>CCNE1<\/jats:italic>\n                      amplification\/Cyclin E1 overexpression. However, Cyclin E1 expression evolution after PARPi has not been studied. We aimed to describe Cyclin E1 expression\/\n                      <jats:italic>CCNE1<\/jats:italic>\n                      copy number in post-PARPi HGOC samples and compare to paired samples from diagnosis and\/or post-neoadjuvant chemotherapy (post-NACT).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty-eight patients with available post-PARPi samples were included; paired samples from diagnosis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200926) and\/or post-NACT (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924) were collected. Cyclin E1 expression was quantified using immunohistochemistry (IHC).\n                      <jats:italic>CCNE1<\/jats:italic>\n                      copy number was evaluated using fluorescent in situ hybridisation (FISH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventy-two percent (26\/36) of HGOC were homologous recombination deficient. Intratumoral Cyclin E1 expression was homogenous in samples from synchronous but anatomically distinct tumour sites. However, Cyclin E1 expression increased significantly between diagnosis and progression post-PARPi (median H-score\u2009=\u2009113\n                      <jats:italic>versus<\/jats:italic>\n                      163, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.034). The proportion of Cyclin E1-high (H-score\u2009\u2265\u2009150) tumours was 31% (8\/26) at diagnosis, 42% (10\/24) post-NACT, and increased significantly to 61% (23\/38) post-PARPi (\n                      <jats:italic>versus<\/jats:italic>\n                      diagnosis;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.024). In contrast, only 10% (2\/20) of Cyclin E1-high HGOC exhibited\n                      <jats:italic>CCNE1<\/jats:italic>\n                      amplification (\u2009\u2265\u20098\n                      <jats:italic>CCNE1<\/jats:italic>\n                      copies).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Cyclin E1 expression in HGOC increases at post-PARPi progression, independently of\n                      <jats:italic>CCNE1<\/jats:italic>\n                      amplification.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03440-y","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:15:26Z","timestamp":1777997726000},"page":"427-435","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Changes in Cyclin E1 expression and CCNE1 amplification in high-grade ovarian carcinomas post-PARP inhibitor exposure"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1674-1888","authenticated-orcid":false,"given":"Alexis","family":"Trecourt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Valent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Yaniz-Galende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Rouleau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Francisco","family":"Grau Bejar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5277-1515","authenticated-orcid":false,"given":"F\u00e9lix","family":"Blanc-Durand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Edmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Le Formal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Genestie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Leary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"3440_CR1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.annonc.2023.05.005","volume":"34","author":"I Ray-Coquard","year":"2023","unstructured":"Ray-Coquard I, Leary A, Pignata S, Cropet C, Gonz\u00e1lez-Mart\u00edn A, Marth C, et al. 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Alexandra Leary reports a relationship with AstraZeneca, MSD, GSK, Abbvie that includes: consulting or advisory and travel reimbursement. AL reports a relationship with Eisai, Regeneron, Zentalis, Pharm&, Apmonia, Owkin for consulting or advisory boards. All fees provided to institution not self. Etienne Rouleau reports a relationship with AstraZeneca, MSD, GSK, Roche, BMS, Clovis, Pharmaand for consulting and advisory board. The other authors declare no potential conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Informed consents were obtained for all patients included in the present study. The FFPE samples from patients included in herein have been declared to the French Ministry of Research (\n                      Gustave Roussy\n                      authorisation number: DC-2020-4158). The present study was approved by the local ethics committee (no. 2025\u2013504) and was conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate and consent for publication","group":{"name":"EthicsHeading","label":"Ethics"}}]}}