{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:58:44Z","timestamp":1760237924643,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T00:00:00Z","timestamp":1656806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Cancer Society","award":["2007-3935"],"award-info":[{"award-number":["2007-3935"]}]},{"name":"Health Foundation Limburg, the Netherlands (HFL)","award":["2007-3935"],"award-info":[{"award-number":["2007-3935"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c\/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI. Methods: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 \u00b5m formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (\u22650.84 \u2264 1.16) was based on the mean CR +\/\u2212 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring &gt; 2 chromosomes of chromosome 1 and\/or 7 (PAN), was established (cut-off value for abnormal PAN \u2265 10%). Results: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%). Conclusions: evaluation criteria for FISH 1c\/7c based on PAN \u2265 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c\/7c detection can be applied in combination with histopathological assessment.<\/jats:p>","DOI":"10.3390\/cancers14133260","type":"journal-article","created":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T22:50:46Z","timestamp":1656888646000},"page":"3260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions"],"prefix":"10.3390","volume":"14","author":[{"given":"Verona E.","family":"Bergshoeff","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, Zuyderland Medical Center, 6419 PC Heerlen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-618X","authenticated-orcid":false,"given":"Maschenka C. A.","family":"Balkenhol","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Pathology, Radboud University Medical Center, 6225 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Haesevoets","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Ruland","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelene N.","family":"Chenault","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Health, Ethics and Society, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik C.","family":"Nelissen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine J.","family":"Peutz","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruud","family":"Clarijs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zuyderland Medical Center, 6419 PC Heerlen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen A. W. M.","family":"Van der Laak","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, 6225 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Takes","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, Radboud University Medical Center, 6225 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-6743","authenticated-orcid":false,"given":"Michiel W.","family":"Van den Brekel","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-9494","authenticated-orcid":false,"given":"Marie-Louise F.","family":"Van Velthuysen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans C. S.","family":"Ramaekers","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3016-2989","authenticated-orcid":false,"given":"Ernst-Jan M.","family":"Speel","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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