PMID- 34696768 OWN - NLM STAT- MEDLINE DCOM- 20220222 LR - 20220222 IS - 1746-1596 (Electronic) IS - 1746-1596 (Linking) VI - 16 IP - 1 DP - 2021 Oct 25 TI - Expression of FRS2 in atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma: an immunohistochemical analysis of 182 cases with genetic data. PG - 96 LID - 10.1186/s13000-021-01161-9 [doi] LID - 96 AB - BACKGROUND: The fibroblast growth factor receptor substrate 2 (FRS2) gene is located close to MDM2 and CDK4 within the 12q13-15 chromosomal region. FRS2 gene was recently found to be consistently amplified in atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DDL), suggesting the detection of FRS2 amplification could be a diagnostic tool for ALT/WDL/DDLs. However, the expression of FRS2 protein and diagnostic value of FRS2 immunohistochemistry (IHC) has not been evaluated in a large cohort of ALT/WDL/DDLs. METHODS: A SNOMED search of hospital surgical pathology files from January 2007 to July 2020 identified 182 ALT/WDL/DDLs with available materials. FRS2 fluorescence in situ hybridization (FISH) and IHC were performed on 182 ALT/WDL/DDLs and 64 control samples. The expression of FRS2 was also compared with that of classic immunomarkers (MDM2 and CDK4) of this tumor entity. RESULTS: This study included 91 ALT/WDLs and 91 DDLs. The FISH results showed 172 of 182 (94.5%) cases were FRS2-amplified, and 10 cases were FRS2-nonamplified. Immunostaining results showed 171 (94.0%) ALT/WDL/DDLs were positive for FRS2 and 11 cases (6.0%) were FRS2-immunonegative. In 172 FRS2-amplified cases, 166 (96.5%) were FRS2-immunopositive, and 6 (3.5%) were negative. Among 10 FRS2-nonamplified ALT/WDL/DDL cases, 5 cases were FRS2-immunonegative, and 5 tumors displayed 1+ staining for this marker. In 64 control cases, none of them exhibited FRS2 amplification. Forty-seven (73.5%) control cases were negative for FRS2 immunostaining, while 17 cases (26.5%) were FRS2-immunopositive. Fifteen of these false positive samples (15/17, 88.2%) showed 1+ positivity and only 2 cases (2/17, 11.8%) displayed 2+ positivity. In ALT/WDL/DDLs, the sensitivity of FRS2 immunostaining was slightly lower than MDM2 (FRS2 vs. MDM2: 94.0% vs 100.0%) and CDK4 (FRS2 vs. CDK4: 94.0% vs 97.0%). However, the specificity of FRS2 (73.5%) was slightly higher than that of MDM2 (67.8%) and CDK4 (64.4%). CONCLUSION: This study indicated that FRS2 IHC had relatively good consistency with FRS2 FISH, suggesting that FRS2 immunostaining could be utilized as an additional screening tool for the diagnosis of ALT/WDL/DDL. It must be emphasized that MDM2/CDK4/FRS2 especially MDM2 FISH remains the gold standard and the most recommended method to diagnose this entity. CI - (c) 2021. The Author(s). FAU - Jing, Wenyi AU - Jing W AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Lan, Ting AU - Lan T AD - Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliate to School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. FAU - Qiu, Yan AU - Qiu Y AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Peng, Ran AU - Peng R AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Lu, Yang AU - Lu Y AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Chen, Huijiao AU - Chen H AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Chen, Min AU - Chen M AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - He, Xin AU - He X AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Chen, Chen AU - Chen C AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. FAU - Zhang, Hongying AU - Zhang H AD - Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan, China. hy_zhang@scu.edu.cn. LA - eng GR - 81972520/national natural science foundation of china/ GR - 81472510/national natural science foundation of china/ GR - 2020YFS0270/sichuan science and technology program/ GR - 2018HXFH011/135 project for disciplines of excellence-clinical research incubation project, west china hospital, sichuan university/ PT - Journal Article DEP - 20211025 PL - England TA - Diagn Pathol JT - Diagnostic pathology JID - 101251558 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Biomarkers, Tumor) RN - 0 (FRS2 protein, human) RN - 0 (Membrane Proteins) SB - IM MH - Adaptor Proteins, Signal Transducing/analysis/*biosynthesis/genetics MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/analysis/genetics/metabolism MH - Female MH - Humans MH - Immunohistochemistry MH - Liposarcoma/genetics/metabolism/*pathology MH - Male MH - Membrane Proteins/analysis/*biosynthesis/genetics MH - Middle Aged MH - Soft Tissue Neoplasms/genetics/metabolism/*pathology MH - Young Adult PMC - PMC8543942 OTO - NOTNLM OT - Atypical lipomatous tumor OT - Dedifferentiated liposarcoma OT - FRS2 OT - Immunohistochemistry OT - Well-differentiated liposarcoma COIS- The authors declare that they have no competing interests. EDAT- 2021/10/27 06:00 MHDA- 2022/02/23 06:00 PMCR- 2021/10/25 CRDT- 2021/10/26 05:33 PHST- 2021/06/12 00:00 [received] PHST- 2021/10/06 00:00 [accepted] PHST- 2021/10/26 05:33 [entrez] PHST- 2021/10/27 06:00 [pubmed] PHST- 2022/02/23 06:00 [medline] PHST- 2021/10/25 00:00 [pmc-release] AID - 10.1186/s13000-021-01161-9 [pii] AID - 1161 [pii] AID - 10.1186/s13000-021-01161-9 [doi] PST - epublish SO - Diagn Pathol. 2021 Oct 25;16(1):96. doi: 10.1186/s13000-021-01161-9.