{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:33:37Z","timestamp":1787646817844,"version":"build-2736575974"},"reference-count":31,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Surg Pathol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"\n Background:<\/jats:bold>\n MD M2<\/jats:italic>\n (\n murine double minute-2<\/jats:italic>\n ) amplification via fluorescence in-situ hybridization (FISH) is the gold standard test used for confirming the diagnosis of atypical lipomatous tumor\/well differentiated liposarcoma and dedifferentiated liposarcoma. It is also used as a screening test in high grade spindle cell or pleomorphic neoplasms.\n MDM2<\/jats:italic>\n FISH is considered positive for amplification when the\n MDM2<\/jats:italic>\n \/CEP12 ratio is greater than 2; however, a ratio between 2 and 3 is considered a \u201clow-level\u201d amplification and raises the possibility of a false positive result; thus, posing a diagnostic dilemma. Another molecular modality, next generation sequencing (NGS) assay, can help in such situations in confirming or excluding the\n M D M 2<\/jats:italic>\n amplification status. Confronted by a number of neoplastic specimens at our institution with \u201clow-level\u201d\n MDM2<\/jats:italic>\n amplification via FISH, we aimed to assess the specificity of fluorescence in situ hybridization (FISH) in such tumors by comparing their NGS assay results and determine an accurate\n MDM2<\/jats:italic>\n amplification status that further aids in diagnosis.\n Methods:<\/jats:bold>\n Tumors with \u201clow-level\u201d\n MDM2<\/jats:italic>\n amplification via FISH, defined as\n MDM2<\/jats:italic>\n \/CEP12 ratio between 2 and 3, and harboring a high grade and\/or pleomorphic morphology were retrospectively retrieved from our institutional archives from the last five years. The retrieved specimens were evaluated for concordant retrospective Oncomine v3 analysis. Oncomine v3 is an institutional NGS assay that covers 161 genes and assesses for DNA mutations, RNA fusions, and copy number alterations including MDM2 gene gain or amplification. The tumors with Oncomine v3 results were compared and the FISH specificity was calculated.\n Results:<\/jats:bold>\n Twenty-seven high grade and\/or pleomorphic tumors with \u201clow-level\u201d\n MDM2<\/jats:italic>\n amplification were retrieved. Eight out of twenty-seven tumors had Oncomine v3 performed on them. The tumors correlated to neoplasms from different lineage types including undifferentiated melanoma, sarcomatoid squamous cell carcinoma, leiomyosarcoma, myxofibrosarcoma, undifferentiated pleomorphic sarcoma, and high-grade poorly differentiated pleomorphic neoplasm. All 8 tumors had a low-level\n MD M2<\/jats:italic>\n amplification ratio ranging between 2.09 and 2.84. Seven out of eight had no\n MD M2<\/jats:italic>\n copy number alteration. One only (leiomyosarcoma) demonstrated\n MD M2<\/jats:italic>\n copy number gain (\u223c5 copies) that did not qualify as amplification due to the \u201c6 copy number\u201d gain cutoff.\n TP53, CDKN2A\/B, PIKC3<\/jats:italic>\n , and\n PTEN<\/jats:italic>\n alterations were the most common genetic aberrations detected by Oncomine v3.\n Conclusion:<\/jats:bold>\n We demonstrated the absence of\n MDM2<\/jats:italic>\n amplification via Oncomine in all our 8 \u201clow-level\u201d MDM2 FISH amplification specimens confirming the FISH results as \u201cfalse positive\u201d with a corresponding FISH specificity rate of 0%. Laboratory measures and utilizing NGS assay when needed, could be implemented when encountering such problematic \u201clow-level\u201d\n MDM2<\/jats:italic>\n amplification specimens to avoid misdiagnosis and misuse of targeted therapy. Future studies are needed to better characterize and investigate such findings.\n <\/jats:p>","DOI":"10.1177\/10668969241295353","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T03:19:53Z","timestamp":1732072793000},"page":"891-900","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Low-Level\n MDM2<\/i>\n Amplification by FISH: An Institutional Experience With a Diagnostic Dilemma"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5556-7376","authenticated-orcid":false,"given":"Rana","family":"Naous","sequence":"first","affiliation":[{"name":"University of Pittsburgh Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa","family":"Hegazy","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.84"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13205230"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.03.013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1947601912455199"},{"key":"e_1_3_2_6_2","article-title":"An update patent review of MDM2-p53 interaction inhibitors (2019-2023)","author":"Twarda-Clapa A.","unstructured":"Twarda-Clapa A. An update patent review of MDM2-p53 interaction inhibitors (2019-2023). Expert Opin Ther Pat. 2024 Oct 22. 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Characterization of the 12q amplicons in lipomatous soft tissue tumors by multiplex ligation-dependent probe amplification-based copy number analysis. 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Fluorescence in situ hybridization for MDM2 amplification as a routine ancillary diagnostic tool for suspected well-differentiated and dedifferentiated liposarcomas: experience at a tertiary center. Sarcoma. 2015 Feb 25;2015:812089. doi: https:\/\/doi.org\/10.1155\/2015\/812089. 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