Abstract
Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma. At times, a fibrosarcomatous transformation marked by a more aggressive clinical behavior may be present. We investigated the natural history and the molecular bases of progression from classic DFSP to the fibrosarcomatous form (FS-DFSP), looking, retrospectively, at the outcome of all patients affected by primary DFSP treated at our institution from 1993 to 2012 and analyzing the molecular profile of 5 DFSPs and 5 FS-DFSPs by an integrated genomics approach (whole transcriptome sequencing, copy number analysis, FISH, qRT-PCR, IHC). The presence of fibrosarcomatous features was identified in 20 (7.6%) patients out of 263 DFSP. All cases were treated with macroscopic complete surgery. A local relapse occurred in 4 of 23 patients who received a microscopic marginal surgery (2 classic DFSP, 2 FS-DFSP), while metastasis affected 2 patients, both FS-DFSP (10% of FS-DFSP), being the first event. DFSP evolution to FS-DFSP was paralleled by a transcriptional reprogramming. The recurrent loss of chromosome 22q appeared to contribute to this phenomenon by promoting the expression of epigenetic regulators, such as EZH2. Loss of the p16/CDKN2A/INK4A locus at 9p was also observed in two FS-DFSP metastatic cases. Implications: FS-DFSP is a rare subgroup among DFSP, with a 10% metastatic risk, that was independent from local recurrence and that was not observed in DFSP, that were all cured by wide surgery. Chromosome 22q deletion might play a role in FS-DFSP, and p16 loss may convey a poor outcome. EZH2 dysregulation was also found and represents a druggable target.
| Original language | English |
|---|---|
| Pages (from-to) | 820-829 |
| Number of pages | 10 |
| Journal | Molecular Cancer Research |
| Volume | 14 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2016 |
Fingerprint
ASJC Scopus subject areas
- Molecular Biology
- Oncology
- Cancer Research
Cite this
Evolution of dermatofibrosarcoma protuberans to DFSP-derived fibrosarcoma : An event marked by epithelial-mesenchymal transition-like process and 22q loss. / Stacchiotti, Silvia; Astolfi, Annalisa; Gronchi, Alessandro; Fontana, Andrea; Pantaleo, Maria A.; Negri, Tiziana; Brenca, Monica; Tazzari, Marcella; Urbini, Milena; Indio, Valentina; Colombo, Chiara; Radaelli, Stefano; Brich, Silvia; Tos, Angelo P Dei; Casali, Paolo G.; Castelli, Chiara; Dagrada, Gian Paolo; Pilotti, Silvana; Maestro, Roberta.
In: Molecular Cancer Research, Vol. 14, No. 9, 01.09.2016, p. 820-829.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evolution of dermatofibrosarcoma protuberans to DFSP-derived fibrosarcoma
T2 - An event marked by epithelial-mesenchymal transition-like process and 22q loss
AU - Stacchiotti, Silvia
AU - Astolfi, Annalisa
AU - Gronchi, Alessandro
AU - Fontana, Andrea
AU - Pantaleo, Maria A.
AU - Negri, Tiziana
AU - Brenca, Monica
AU - Tazzari, Marcella
AU - Urbini, Milena
AU - Indio, Valentina
AU - Colombo, Chiara
AU - Radaelli, Stefano
AU - Brich, Silvia
AU - Tos, Angelo P Dei
AU - Casali, Paolo G.
AU - Castelli, Chiara
AU - Dagrada, Gian Paolo
AU - Pilotti, Silvana
AU - Maestro, Roberta
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma. At times, a fibrosarcomatous transformation marked by a more aggressive clinical behavior may be present. We investigated the natural history and the molecular bases of progression from classic DFSP to the fibrosarcomatous form (FS-DFSP), looking, retrospectively, at the outcome of all patients affected by primary DFSP treated at our institution from 1993 to 2012 and analyzing the molecular profile of 5 DFSPs and 5 FS-DFSPs by an integrated genomics approach (whole transcriptome sequencing, copy number analysis, FISH, qRT-PCR, IHC). The presence of fibrosarcomatous features was identified in 20 (7.6%) patients out of 263 DFSP. All cases were treated with macroscopic complete surgery. A local relapse occurred in 4 of 23 patients who received a microscopic marginal surgery (2 classic DFSP, 2 FS-DFSP), while metastasis affected 2 patients, both FS-DFSP (10% of FS-DFSP), being the first event. DFSP evolution to FS-DFSP was paralleled by a transcriptional reprogramming. The recurrent loss of chromosome 22q appeared to contribute to this phenomenon by promoting the expression of epigenetic regulators, such as EZH2. Loss of the p16/CDKN2A/INK4A locus at 9p was also observed in two FS-DFSP metastatic cases. Implications: FS-DFSP is a rare subgroup among DFSP, with a 10% metastatic risk, that was independent from local recurrence and that was not observed in DFSP, that were all cured by wide surgery. Chromosome 22q deletion might play a role in FS-DFSP, and p16 loss may convey a poor outcome. EZH2 dysregulation was also found and represents a druggable target.
AB - Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma. At times, a fibrosarcomatous transformation marked by a more aggressive clinical behavior may be present. We investigated the natural history and the molecular bases of progression from classic DFSP to the fibrosarcomatous form (FS-DFSP), looking, retrospectively, at the outcome of all patients affected by primary DFSP treated at our institution from 1993 to 2012 and analyzing the molecular profile of 5 DFSPs and 5 FS-DFSPs by an integrated genomics approach (whole transcriptome sequencing, copy number analysis, FISH, qRT-PCR, IHC). The presence of fibrosarcomatous features was identified in 20 (7.6%) patients out of 263 DFSP. All cases were treated with macroscopic complete surgery. A local relapse occurred in 4 of 23 patients who received a microscopic marginal surgery (2 classic DFSP, 2 FS-DFSP), while metastasis affected 2 patients, both FS-DFSP (10% of FS-DFSP), being the first event. DFSP evolution to FS-DFSP was paralleled by a transcriptional reprogramming. The recurrent loss of chromosome 22q appeared to contribute to this phenomenon by promoting the expression of epigenetic regulators, such as EZH2. Loss of the p16/CDKN2A/INK4A locus at 9p was also observed in two FS-DFSP metastatic cases. Implications: FS-DFSP is a rare subgroup among DFSP, with a 10% metastatic risk, that was independent from local recurrence and that was not observed in DFSP, that were all cured by wide surgery. Chromosome 22q deletion might play a role in FS-DFSP, and p16 loss may convey a poor outcome. EZH2 dysregulation was also found and represents a druggable target.
UR - http://www.scopus.com/inward/record.url?scp=84987858959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84987858959&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-16-0068
DO - 10.1158/1541-7786.MCR-16-0068
M3 - Article
AN - SCOPUS:84987858959
VL - 14
SP - 820
EP - 829
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 9
ER -