{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:04Z","timestamp":1792087984580,"version":"4.4.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Liposarcomas including atypical lipomatous tumors (ALT)\/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPSs) display a histomorphological spectrum with their several diagnostic mimics.\n                      <jats:italic toggle=\"yes\">Murine double minute 2(MDM2)<\/jats:italic>\n                      gene amplification characterizes ALT\/WDLPS and DDLPS. Presently, there is no documented study from our subcontinent on the validation of\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      gene testing in these tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods:<\/jats:title>\n                    <jats:p>\n                      Twenty-eight cases, diagnosed as ALT\/WDLPS (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5) and DDLPSs (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 23), along with 10 other tumors were tested for\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      gene amplification, using fluorescence\n                      <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                      hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, diagnosed as ALT\/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 immunostaining. Twenty tumors were tested for p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      immunostaining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as DDLPSs, 19 displayed\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      gene amplification. Among the 5 cases diagnosed as ALT\/WDLPS, four showed\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      gene amplification. Finally, 19 cases were confirmed as DDLPS and 4 as ALT\/WDLPS. Furthermore, 7\/19 cases confirmed as DDLPS and all 4 cases as ALT\/WDLPS tested for\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      immunostaining, displayed its diffuse immunoexpression, while a single case of DDLPS showed its focal immunostaining. None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 DDLPSs and 4 cases of ALT\/WDLPS displayed p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      immunostaining. The sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in ALT\/WDLPS, and specificity was 100%. The sensitivity for\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      gene amplification was 94.7% in cases of DDLPS and 100% in cases of ALT\/WDLPS. The sensitivity for p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      was 100%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      This constitutes the first sizable study on MDM2 testing in ALT\/WDLPS and DDLPS from our subcontinent using TMAs.\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      gene amplification testing continues as the diagnostic gold standard for ALTs\/WDLPSs and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 clone) and p16\n                      <jats:sup>INK4a<\/jats:sup>\n                      immunostaining, together seem useful for triaging cases for FISH.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijpm.ijpm_1238_20","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T15:49:55Z","timestamp":1724946595000},"page":"65-75","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Detection of MDM2 gene amplification on tissue microarray-based Fluorescence In-Situ Hybridization (FISH) in well-differentiated and dedifferentiated liposarcomas, displaying a wide morphological 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Pathol"},{"key":"R8-13-20240829","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/modpathol.2008.84","article-title":"Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms","volume":"21","author":"Weaver","year":"2008","journal-title":"Mod Pathol"},{"key":"R9-13-20240829","doi-asserted-by":"crossref","first-page":"812089","DOI":"10.1155\/2015\/812089","article-title":"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","volume":"2015","author":"Thway","year":"2015","journal-title":"Sarcoma"},{"key":"R10-13-20240829","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/PAS.0b013e3182417330","article-title":"Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other 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