Key result
Collagenous-dominant dedifferentiated liposarcomas are linked to greater DDR2 amplification and SMA expression than myxoid-dominant tumors.
Why the study?
Dedifferentiated liposarcoma exhibits substantial morphologic heterogeneity, and this study aimed to determine whether prominent stromal patterns are associated with distinct immunophenotypic and genomic profiles.
Observational (n=19)
Prominent stromal patterns in dedifferentiated liposarcoma reflect biologically meaningful subsets with distinct immunophenotypic features and secondary genomic alterations, such as DDR2 amplification in collagenous-dominant tumors.
Stromal patterns may delineate DDLPS subtypes; leaves open whether DDR2 amplification informs targeted therapy selection.
Background/Aim: Dedifferentiated liposarcoma (DDL) is defined by amplification of chromosome 12q13-15 but exhibits substantial morphologic heterogeneity, including variable stromal composition. This study aimed to determine whether prominent stromal patterns in DDL are associated with distinct immunophenotypic and genomic profiles. Patients and Methods: Nineteen surgically resected DDLs were evaluated for histologic features, immunophenotype, and targeted genomic alterations using next-generation sequencing. Associations between stromal pattern, immunohistochemistry, copy number alterations, and clinical outcome were analyzed. Results: All cases demonstrated MDM2 amplification and strong nuclear MDM2 expression, with frequent co-amplification of CDK4. Beyond canonical 12q alterations, recurrent amplifications were identified, including 1q23 (DDR2), 5p15 (TERT), and 12q13 (STAT6). Notably, DDR2 amplification was significantly enriched in collagenous-dominant DDLs compared with myxoid-dominant tumors. Stromal pattern correlated with immunophenotype, with collagenous-dominant tumors showing frequent SMA expression and absence of CD34, whereas myxoid-dominant tumors more frequently expressed CD34. High mitotic activity and mFNCLCC grade 3, but not stromal pattern, were associated with adverse outcome. Conclusion: Prominent stromal patterns in DDL reflect biologically meaningful subsets associated with distinct immunophenotypic features and secondary genomic alterations. In particular, enrichment of DDR2 amplification in collagenous-dominant DDL suggests a potential link between collagen-associated signaling pathways and stromal morphogenesis in this tumor.
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CHOI et al. (2026) conducted an observational in Dedifferentiated liposarcoma (n=19). Collagenous-dominant stromal pattern vs. Myxoid-dominant stromal pattern was evaluated on Immunophenotypic and genomic profiles (DDR2 amplification, SMA, CD34 expression). Collagenous-dominant dedifferentiated liposarcomas were significantly enriched for DDR2 amplification and SMA expression compared with myxoid-dominant tumors.
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