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Published on: April 3, 2026
Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib
Grant A McArthur1, George D Demetri, Allan van Oosterom
1Peter MacCallum Cancer Centre, East Melbourne, Australia. grant.mcarthur@petermac.org
Purpose:
The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib.
Patients And Methods:
We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease.
Results:
Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism.
Conclusion:
Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.
Insights
Imatinib shows clinical activity in dermatofibrosarcoma protuberans (DFSP) with the t(17;22) translocation. However, fibrosarcomatous DFSP variants lacking this translocation may not respond to imatinib treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous malignancy.
- DFSP often involves a characteristic translocation t(17;22), leading to dysregulated platelet-derived growth factor-B (PDGFB) expression.
- Understanding the molecular underpinnings of DFSP is crucial for targeted therapy development.
Purpose of the Study:
- To evaluate molecular, cytogenetic, and kinase activation profiles in DFSP.
- To correlate these biologic parameters with clinical response to imatinib therapy.
- To investigate the efficacy of imatinib in localized and metastatic DFSP.
Main Methods:
- Analysis of radiologic and clinical response to imatinib (400 mg BID) in 10 patients with DFSP.
- Molecular and cytogenetic analysis of tumor samples.
- Assessment of platelet-derived growth factor receptor-beta (PDGFR-β) phosphorylation.
Main Results:
- Eight patients with locally advanced DFSP and t(17;22) showed clinical responses to imatinib, with four achieving complete response.
- Metastatic DFSP cases exhibited complex karyotypes; one with t(17;22) had a partial response, while another without t(17;22) showed no response.
- Minimal PDGFR-β phosphorylation was observed despite a PDGFB autocrine loop.
Conclusions:
- Imatinib demonstrates clinical activity in DFSP harboring the t(17;22) translocation, including metastatic forms.
- Fibrosarcomatous DFSP variants lacking t(17;22) may exhibit resistance to imatinib.
- Further research into resistance mechanisms and alternative therapeutic strategies for non-responsive DFSP is warranted.
