The pathological significance of DNA damage-inducible transcript 3 immunohistochemistry in the diagnosis of myxoid liposarcoma.

BACKGROUND

Myxoid liposarcoma (MLS) is a distinct subtype of liposarcoma characterised by recurrent FUS-DDIT3 or EWSR1-DDIT3 gene fusions and distinctive histological features. DNA damage-inducible transcript 3 (DDIT3) is a key downstream mediator of these fusions and contributes to sarcoma development by disrupting adipocytic differentiation. In this study, we assessed the diagnostic value and biological relevance of DDIT3 by combining immunohistochemistry (IHC) with quantitative real-time polymerase chain reaction (qRT-PCR).

METHODS

The study included 128 soft tissue tumours, comprising 45 cases of MLS and 83 histological mimics. DDIT3 expression was evaluated by IHC, and transcript-level expression was analysed using qRT-PCR. FUS-DDIT3 fusion transcripts were assessed and associations with clinicopathological features and FNCLCC tumour grade were analysed.

RESULTS

DDIT3 IHC was positive in 42/45 (93.3%) MLS cases and 3/83 (3.6%) histological mimics (P < 0.001), yielding a sensitivity of 93.3%, specificity of 96.4%, positive predictive value of 93.3%, and negative predictive value of 96.4%. All cases with classic MLS morphology showed positive nuclear DDIT3 staining, whereas the three non-positive MLS cases occurred within the high-grade/round-cell subgroup. Among the mimics, DDIT3 positivity was observed only in 3 of 5 Ewing sarcoma cases. qRT-PCR demonstrated variation in FUS: DDIT3 transcript expression among the analysed cases; however, transcript-level expression did not uniformly parallel immunohistochemical protein detection.

CONCLUSIONS

DDIT3 is a highly sensitive and specific marker for the diagnosis of MLS. The concordance between protein and transcript expression highlights the biological relevance of DDIT3 and supports its use as a practical, cost-effective adjunct to molecular testing in routine diagnostic practice.