Disease relevance of Dermatofibrosarcoma

• PURPOSE: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade, cutaneous sarcoma with autocrine overproduction of the platelet-derived growth factor (PDGF) beta-chain from gene rearrangement as a key pathogenetic factor, now susceptible of molecular-targeted therapy [1].
• Recently, the COL1A1-PDGFB chimeric gene resulting from a reciprocal translocation, t(17;22), and/or a supernumerary ring chromosome, r(17;22), has been identified, not only in conventional dermatofibrosarcoma protuberans (DFSP) but also in areas of DFSP with progression to fibrosarcoma (so-called fibrosarcomatous transformation) (FS-DFSP) [2].
• Other tumours included carcinoma of the pancreas (2 rats), leiomyoma of the small intestine (1 rat) and a large dermatofibrosarcoma (1 rat) [3].
• Claudin-1 expression was not noted in any cases of dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, desmoplastic fibroblastoma, or fibromatosis [4].
• In contrast to atrophic dermatofibroma all three atrophic dermatofibrosarcoma protuberans showed a consistently uniform profile: CD34 positive, factor XIIIa and metallothionein negative [5].

High impact information on Dermatofibrosarcoma

• Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma [6].
• Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225 [7].
• PURPOSE: Dermatofibrosarcoma protuberans is caused by activation of the platelet-derived growth factor B (PDGFB) receptor, a transmembrane tyrosine kinase [8].
• PATIENTS AND METHODS: A patient with unresectable, metastatic dermatofibrosarcoma protuberans received imatinib mesylate (400 mg bid) [8].
• The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB [9].

Chemical compound and disease context of Dermatofibrosarcoma

• Imatinib GIST keeps finding new indications: successful treatment of dermatofibrosarcoma protuberans by targeted inhibition of the platelet-derived growth factor receptor [10].
• We investigated the response of dermatofibrosarcoma protuberans to the tyrosine kinase inhibitor imatinib mesylate [8].
• Increased DNA synthesis of dermatofibrosarcoma protuberans cells was abolished by genistein, a tyrosine kinase inhibitor, or by PD98059, a specific extracellular signal related kinase pathway inhibitor, but not by calphostin C, a protein kinase C inhibitor [11].
• Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues [12].
• Immunohistochemically, the tumor stained diffusely for vimentin and CD34, a surface glycoprotein expressed by some mesenchymal neoplasms including dermatofibrosarcoma protuberans [13].

Biological context of Dermatofibrosarcoma

• Microsatellite instability and p53 mutation associated with tumor progression in dermatofibrosarcoma protuberans [14].
• A repeat biopsy showed dermatofibrosarcoma protuberans, with a storiform spindle cell proliferation with positive CD34 staining [15].
• EMA+ cells in dermatofibrosarcoma protuberans. A study of 11 tumors suggesting perineurial cell differentiation [16].

Anatomical context of Dermatofibrosarcoma

• Strong and generalized CD34 positivity was also found in most dermatofibrosarcoma protuberans (11 of 12, 92%) and occasional smooth-muscle tumors (leiomyomas 2 of 11, 18%; leiomyosarcomas 2 of 11, 18%) [17].
• However, focal CD34 staining and involvement of superficial subcutaneous tissue raised concern regarding an early dermatofibrosarcoma protuberans developing in a dermatofibroma [18].

Gene context of Dermatofibrosarcoma

• The novel fusion partners appear well suited to drive USP6 transcription in the bone/mesenchymal context: osteomodulin is expressed strongly in osteoblastic lineages, and the COL1A1 promoter has an oncogenic role in the mesenchymal cancer dermatofibrosarcoma protuberans [19].
• Dermatofibrosarcoma protuberans with COL1A1 (exon 18) -PDGFB (exon 2) fusion transcript [20].
• Differential expression of HMGA1 and HMGA2 in dermatofibroma and dermatofibrosarcoma protuberans: potential diagnostic applications, and comparison with histologic findings, CD34, and factor XIIIa immunoreactivity [21].
• For comparison, they examined CD34 antigen expression in these lesions, which has been shown to be a useful marker in differentiating dermatofibrosarcoma protuberans from dermatofibroma [22].
• Dermatofibrosarcoma protuberans with fibrosarcomatous areas. Molecular abnormalities of the p53 pathway in fibrosarcomatous transformation of dermatofibrosarcoma protuberans [23].

Analytical, diagnostic and therapeutic context of Dermatofibrosarcoma

• OBJECTIVE: Our purpose was to study by immunohistochemistry the expression of ST3 in dermatofibromas and dermatofibrosarcoma protuberans (DFP) [24].
• CD44 and hyaluronate in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans [25].
• CONCLUSIONS: These findings confirm prior reports that negative staining with CD34, Factor XIIIa and S-100 can help differentiate scars from dermatofibrosarcoma protuberans, dermatofibroma and desmoplastic malignant melanoma, respectively [26].
• Its efficacy in treating BCC and SCC has led clinicians to explore the role of Mohs micrographic surgery in the management of less common cutaneous neoplasms, such as melanoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans, extramammary Paget's disease, and microcystic adnexal carcinoma [27].

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