Genomic gains of COL1A1‐PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans

Abstract

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells.

Molecular diagnosis of dermatofibrosarcoma protuberans: A comparison between reverse transcriptase‐polymerase chain reaction and fluorescence in situ hybridization methodologies

“…We thus analyzed if the presence of COL1A1/PDGFB extra fusion signals was frequently observed in DFSP-FS. In agreement with Stacchiotti et al (2011), no significant relationship was observed in contrast to previously reported series, including earlier results from our group (Abbott et al, 2006;Macarenco et al, 2008;Segura et al, 2011). The limited number of such cases included in these studies may explain these negative results.…”

“…A positive result using DCDF probes requires two fusion signals, an event that is very unlikely to occur by chance. A limited number of studies on DFSP using FISH techniques has been reported and most of them were small series using both PDGFB break-apart (Abbott et al, 2006;Macarenco et al, 2008;Patel et al, 2008) and DCDF COL1A1/PDGFB probes (Craver et al, 2006;Maire et al, 2007;Segura et al, 2011). Regarding PDGFB break-apart probes, the largest series reported included 27 patients and the presence of the translocation was observed in 96% of cases (Patel et al, 2008).…”

“…In our previous experience (Llombart et al, accepted for publication), we observed that 76% is detected using RT-PCR in paraffin embedded tissue samples. FISH has been performed using both PDGFB break-apart and COL1A1/PDGFB dual color dual fusion (DCDF) non-commercial probe strategies (Abbott et al, 2006;Craver et al, 2006;Maire et al, 2007;Macarenco et al, 2008;Patel et al, 2008;Segura et al, 2011). It has been postulated that dual fusion probes are better than break-apart regarding sensitivity because their false positive rate in normal tissues is very low (Ventura et al, 2006).…”

Current treatment options in dermatofibrosarcoma protuberans

“…The Giant cell Wbroblastoma is deWned as a histologic variant of DFSP that primarily aVects children. Both variants occur on the same localizations and have a similar morphology, an identical chromosomal translocation, and CD34 positivity (Terrier-Lacombe et al 2003;Diwan et al 2008;Macarenco et al 2008).…”

Identification of t(17;22)(q22;q13) (COL1A1/PDGFB) in dermatofibrosarcoma protuberans by fluorescence in situ hybridization in paraffin-embedded tissue microarrays

“…FISH technique is simpler, more effective, and less time consuming than RT-PCR in the detection of COL1A1/PDGFB rearrangements in DFSP and may have some diagnostic and therapeutic relevance in daily practice. FISH analysis has been performed in a small series of cases [17][18][19][20][21], and the pattern of the translocation has only occasionally been analyzed [19,21]. Therefore, a clinical, histologic, and FISH study in 40 tissue samples of patients with DFSP using paraffinembedded tissue microarrays (TMAs) was performed.…”