MDM2 and DDIT3 coexpression in dedifferentiated liposarcoma with myxoid features: a retrospective cohort study

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Ates K. E., GÖNLÜŞEN G., ERDOĞAN Ş., MİRİOĞLU A.

Scientific Reports, cilt.16, sa.1, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1038/s41598-026-53766-z
  • Dergi Adı: Scientific Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals, Zoological Record, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
  • Anahtar Kelimeler: DDIT3, Dedifferentiated liposarcoma, Differential diagnosis, Immunohistochemistry, MDM2, Myxoid features, Prognosis
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Çukurova Üniversitesi Adresli: Evet

Özet

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.