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Original Investigation |

A Novel Chromosomal Translocation Associated With COL1A2-PDGFB Gene Fusion in Dermatofibrosarcoma Protuberans PDGF Expression as a New Diagnostic Tool

Ikumi Nakamura, MD1; Yoshiyuki Kariya, MD, PhD1; Etsuko Okada, MD, PhD2; Masahito Yasuda, MD, PhD2; Shigetaka Matori, MD1; Osamu Ishikawa, MD, PhD2; Hiroshi Uezato, MD, PhD1; Kenzo Takahashi, MD, PhD1
[+] Author Affiliations
1Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
2Department of Dermatology, Graduate School of Medicine, Gunma University, Maebashi, Japan
JAMA Dermatol. 2015;151(12):1330-1337. doi:10.1001/jamadermatol.2015.2389.
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Importance  Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer that develops in the deep dermis to subcutaneous adipose tissues. A COL1A1-PDGFB gene fusion, leading to the constitutive expression of PDGFB, is the tumorigenic mechanism in most DFSP cases.

Objectives  To evaluate the specificity of PDGFB expression as a diagnostic marker of DFSP and to determine whether other pathomechanisms (ie, gene fusions) exist in patients with DFSP without the COL1A1-PDGFB fusion gene.

Design, Setting, and Participants  All patients with DFSP registered in the pathologic database of the University of the Ryukyus from January 1, 1997, through December 31, 2013, and Gunma University from January 1, 1996, through December 31, 2011, were included in this analysis. Samples were obtained from 30 patients presenting with DFSP tumors. We examined the clinicopathologic characteristics and the expression of PDGFB, PDGFRβ, PDGFRα, CD34, nestin, factor XIIIa, fibronectin, α–smooth muscle actin, S-100 protein, and Ki-67 in 30 DFSP cases and 48 non-DFSP mesenchymal tumor cases by immunohistochemical analysis. We then analyzed tumor tissues for the presence of the COL1A1-PDGFB fusion gene. We also tested whether other genes enriched in fibroblasts formed fusion products with PDGFB by reverse transcription–polymerase chain reaction analysis, using gene-specific primers.

Main Outcomes and Measures  We aimed to analyze tumor tissues for the presence of the COL1A1-PDGFB fusion gene to investigate expression of PDGFB in DFSP tumors.

Results  PDGFB expression was detected in 28 (93%) of 30 patients with DFSP. PDGFB was not homogenously expressed in DFSP tumor cells, whereas CD34 and nestin were often expressed throughout the tumor mass. In 1 DFSP tumor, the COL1A1-PDGFB fusion gene was not detected even though PDGFB was expressed. We identified a novel COL1A2-PDGFB fusion gene in this tumor.

Conclusions and Relevance  Our findings indicate that PDGFB protein is expressed in most DFSP tumors and may be a useful diagnostic tool when used in conjunction with CD34 and nestin expression analysis. These PDGFB expression data, in addition to our discovery of a novel PDGF fusion gene, strongly support the concept that DFSP is a PDGFB-dependent tumor type.

Figures in this Article


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Figure 1.
Representative Expression Pattern of PDGFB in Dermatofibrosarcoma Protuberans (DFSP) Specimens

A and B, PDGFB expression was detected in the tumor cells and in the stroma. C, PDGFB was peripherally expressed in patient 3. D, PDGFB was focally expressed in patient 21 or diffusely expressed in DFSP. A-D, 3,3′-diaminobenzidine. Scale bars indicate 100 μm (A and B) and 1000 μm (C and D).

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Figure 2.
Comparison of PDGFB and PDGFRβ Expression in Dermatofibrosarcoma Protuberans Specimens

A and B, Patient 28: PDGFB (A) and PDGFRβ (B) were expressed in the same regions. C and D, Patient 23 PDGFB (C) was expressed peripherally, whereas PDGFRβ (D) was expressed centrally. A and C, 3-amino-9-ethylcarbazole; B and D, 3,3′-diaminobenzidine. Scale bar indicates 1000 μm (A-D).

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Figure 3.
COL1A2-PDGFB Fusion Gene in Patient 9

A, Amplification products were detected using the COL1A2 exons 1, 5, 11, 17, and 23 and PDGFB exon 2 primers. B, The fusion protein was generated with a matched reading frame between COL1A2 exon 26 and PDGFB exon 2. bp indicates base pair.

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Figure 4.
Histologic Characteristics of Dermatofibrosarcoma Protuberans Containing the COL1A2-PDGFB Fusion Gene

A and B, Tumor cells expressed CD34 (A [3,3′-diaminobenzidine] and PDGFB (B [3-amino-9-ethylcarbazole]). Tumor cells at the margins expressed higher levels of PDGFB (B [arrowhead] and C), whereas nontumorous fibroblasts did not (B [asterisk] and D). C and D, 3-amino-9-ethylcarbazole. Scale bars indicate 1000 μm (A and B) and 100 μm (C and D).

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