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Purpose <p><i>MDM2</i> and <i>CDK4</i> amplifications are well-established diagnostic markers in liposarcoma, but the clinical relevance of their co-amplification remains underexplored. This study evaluates their amplification characteristics and combined prognostic impact to inform risk stratification and patient management.</p> Methods <p>Fluorescence in situ hybridisation (FISH) was performed on formalin-fixed paraffin-embedded samples of liposarcoma or benign lipomatous tumours (≥ 10&#xa0;cm) histologically diagnosed at Hospital Pakar Universiti Sains Malaysia. Recurrence-free (RFS) and metastasis-free survival (MFS) across amplifications were determined using Kaplan–Meier. Recurrence associations with clinicopathological variables were examined using Cox regression.</p> Results <p>Among 86 cases, 27% were liposarcoma and 73% were benign tumours by FISH. Co-amplification (13%) was observed in all dedifferentiated liposarcoma (DDLS) and half of atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLS) cases. <i>MDM2</i> amplification without <i>CDK4</i> (6%) was seen in ALT. Myxoid liposarcoma, pleomorphic liposarcoma, and benign tumours showed no amplification (81%). DDLS had higher <i>MDM2</i> and <i>CDK4</i> amplification ratios (4.4 and 2.8, respectively) than ALT/WDLS (2.9 and 2.6, respectively), with <i>MDM2</i> consistently exceeding <i>CDK4</i>. Co-amplification associated with the shortest median RFS (34&#xa0;months; p = 0.002) and MFS (83&#xa0;months; p = 0.003). Surgery with chemotherapy (p = 0.042; HR = 26.50) associated with recurrence, while <i>MDM2</i>/<i>CDK4</i> amplification was not an independent prognostic factor.</p> Conclusion <p><i>MDM2</i> amplification was more consistent and quantitatively higher than <i>CDK4</i>, supporting its central role in tumourigenesis. While <i>MDM2/CDK4</i> co-amplification was associated with poorer outcomes, it lacked independent prognostic value, reflecting the potential influence of other clinical variables. Nevertheless, co-amplification may hold clinical relevance in identifying high-risk liposarcoma subgroups.</p>

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Prognostic Implications of MDM2 and CDK4 Co-amplification in Liposarcoma: Insights from FISH analysis for Translational Oncology

  • 期刊论文

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  • 发表日期：

    2025年7月16日

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  • Jessinntha James,
  • Aidy Irman Yajid,
  • Sahran Yahaya,
  • Sarimah Abdullah,
  • Sharifah Emilia Tuan Sharif

摘要

Purpose

MDM2 and CDK4 amplifications are well-established diagnostic markers in liposarcoma, but the clinical relevance of their co-amplification remains underexplored. This study evaluates their amplification characteristics and combined prognostic impact to inform risk stratification and patient management.

Methods

Fluorescence in situ hybridisation (FISH) was performed on formalin-fixed paraffin-embedded samples of liposarcoma or benign lipomatous tumours (≥ 10 cm) histologically diagnosed at Hospital Pakar Universiti Sains Malaysia. Recurrence-free (RFS) and metastasis-free survival (MFS) across amplifications were determined using Kaplan–Meier. Recurrence associations with clinicopathological variables were examined using Cox regression.

Results

Among 86 cases, 27% were liposarcoma and 73% were benign tumours by FISH. Co-amplification (13%) was observed in all dedifferentiated liposarcoma (DDLS) and half of atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLS) cases. MDM2 amplification without CDK4 (6%) was seen in ALT. Myxoid liposarcoma, pleomorphic liposarcoma, and benign tumours showed no amplification (81%). DDLS had higher MDM2 and CDK4 amplification ratios (4.4 and 2.8, respectively) than ALT/WDLS (2.9 and 2.6, respectively), with MDM2 consistently exceeding CDK4. Co-amplification associated with the shortest median RFS (34 months; p = 0.002) and MFS (83 months; p = 0.003). Surgery with chemotherapy (p = 0.042; HR = 26.50) associated with recurrence, while MDM2/CDK4 amplification was not an independent prognostic factor.

Conclusion

MDM2 amplification was more consistent and quantitatively higher than CDK4, supporting its central role in tumourigenesis. While MDM2/CDK4 co-amplification was associated with poorer outcomes, it lacked independent prognostic value, reflecting the potential influence of other clinical variables. Nevertheless, co-amplification may hold clinical relevance in identifying high-risk liposarcoma subgroups.