Key result
DDIT3 expression was present in 23.9% of dedifferentiated liposarcomas with myxoid features and was associated with extensive myxoid components, but showed no significant impact on local recurrence (RR 0.85) or overall survival.
Why the study?
DDIT3 immunohistochemistry has been reported in dedifferentiated liposarcoma mimicking myxoid liposarcoma, but its frequency, staining pattern, and clinical significance remain poorly characterised.
Does DDIT3 expression have prognostic significance in dedifferentiated liposarcoma with myxoid features?
Cohort (n=46)
No
Does DDIT3 expression have prognostic significance in dedifferentiated liposarcoma with myxoid features?
Effect estimate: RR 0.85 (95% CI 0.29-2.51)
Absolute Event Rate: 37.5% vs 44%
p-value: p=0.337
DDIT3 positivity in DDLPS with myxoid features is predominantly focal and low-intensity, distinguishing it from true MLPS, and lacks prognostic significance.
DDIT3 positivity lacks prognostic significance in DDLPS with myxoid features; leaves open its diagnostic utility versus MLPS in larger cohorts.
Dedifferentiated liposarcoma (DDLPS) can exhibit myxoid morphology that closely mimics myxoid liposarcoma (MLPS), creating significant diagnostic challenges. DDIT3 immunohistochemistry (IHC), a specific marker for MLPS, has been reported in a subset of DDLPS cases, but its frequency, staining pattern, and clinical significance remain poorly characterised. We retrospectively analysed 46 DDLPS cases with prominent myxoid features (≥ 10% myxoid component) confirmed by MDM2 IHC and fluorescence in situ hybridisation (FISH), treated at a single tertiary centre between January 2007 and January 2026. DDIT3 IHC was scored using a semiquantitative H-score system. DDIT3 positivity occurred in 11 of 46 cases (23.9%, 95% CI: 12.6–38.8%), predominantly as focal staining (9/11, 81.8%). All DDIT3-positive cases exhibited myxoid components comprising > 25% of tumour volume, versus variable myxoid extent in DDIT3-negative cases (p < 0.001). Mean H-score in DDIT3-positive cases was 48.6 ± 32.4 (range 15–120), significantly lower than in true MLPS controls (mean 278 ± 22, p < 0.001). Tumour size > 15 cm significantly increased the risk of local recurrence (risk ratio [RR] = 2.31, 95% CI: 1.02–5.24, p = 0.048). DDIT3 expression showed no significant association with local recurrence (p = 0.337), distant metastasis (p = 0.825), or mortality (p = 0.805). Kaplan–Meier analysis revealed no significant difference in overall survival (log-rank p = 0.782) or recurrence-free survival (log-rank p = 0.614) between DDIT3-positive and DDIT3-negative groups. DDIT3 positivity in DDLPS with myxoid features predominantly produces focal, low-intensity staining that distinguishes it from true MLPS. DDIT3 expression reflects chromosomal co-amplification within the 12q13-15 amplicon and lacks prognostic significance. Combined MDM2 and DDIT3 IHC with careful morphological assessment aids differential diagnosis, particularly when molecular testing is unavailable.
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Ateş et al. (2026) conducted a cohort in Dedifferentiated liposarcoma with myxoid features (n=46). DDIT3 expression vs. DDIT3-negative was evaluated on Local recurrence (RR 0.85, 95% CI 0.29-2.51, p=0.337). DDIT3 expression was present in 23.9% of dedifferentiated liposarcomas with myxoid features and was associated with extensive myxoid components, but showed no significant impact on local recurrence (RR 0.85) or overall survival.
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