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

Abstract

Dermatofibrosarcoma protuberans (DFSP) is characterized by the presence of the t(17;22)(q22;q13) that leads to the fusion of the COL1A1 and PDGFB genes. This translocation can be detected by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) techniques. We have evaluated the usefulness of a dual color dual fusion FISH probe strategy for COL1A1/PDGFB detection in a series of 103 archival DFSPs and compared the obtained results with RT-PCR analyses. FISH and RT-PCR were carried out on paraffin embedded tissue samples. Regarding the RT-PCR approach, all COL1A1 exons and exon 2 of PDGFB were evaluated. Sensitivity, specificity, positive and negative predictive values were assessed considering the histological diagnosis as the gold standard. We also analyzed the relationship between the genetic findings and the clinicopathological variables of the tumors. The COL1A1/PDGFB translocation was detected in 93% of DFSP. Both techniques showed a similar specificity (100%), but FISH was more sensitive than RT-PCR (90% vs. 72%). Regarding, clinicopathological features, a higher percentage of positive cells detected by FISH was significantly associated with the fibrosarcomatous DFSP variant (P < 0.001). Interestingly, all CD34 negative DFSP (n = 5) were positive for COL1A1/PDGFB translocation by both techniques. In conclusion, the majority of DFSP harbor the COL1A1/PDGFB translocation and FISH technique should be recommended as a routine diagnostic tool, especially in cases showing unusual histopathological subtypes and/or immunohistochemical features.

Evolution of Dermatofibrosarcoma Protuberans to DFSP-Derived Fibrosarcoma: An Event Marked by Epithelial–Mesenchymal Transition–like Process and 22q Loss

“…Previously, fibrosarcomatous transformation of DFSP had been correlated to the amplification of COL1A1-PDGFB fusion, an association that we and others failed to confirm (4,22). Also in the series here analyzed, both DFSP and FS-DFSP shared extra copies of the chromosome material flanking the COL1A1-PDGFB breakpoint, ruling out a major role for COL1A1-PDGFB amplification in fibrosarcomatous evolution.…”

“…FISH analyses indicated that the pattern observed was compatible with the loss of one copy of nontranslocated chromosome 22. To the best of our knowledge, 22q loss, although occasionally reported (22)(23)(24)(25)(26)(27)(28), has never been associated to fibrosarcomatous evolution.…”

“…DFSP and FS-DFSP are characterized by the reciprocal chromosome translocation t(17;22)(q22;q13.1) or, more often, supernumerary ring chromosome or markers derived from t (17;22), in which the collagen type Ia1 gene (COL1A1) on chromosome 17 is fused to the platelet-derived growth factor b-chain gene (PDGFB) on chromosome 22. The resulting upregulation of the PDGFB protein activates the PDGFB receptor (PDGFRB), inducing tumor growth through an autocrine-paracrine loop (4,6,7).…”

Immunohistochemistry in Dermatopathology

“…46,238,[251][252][253][254] Most DFSPs harbor the COL1A1-PDGFB translocation, and FISH can be used in cases showing confusing histopathologic and/or immunohistochemical features. 255 Positivity with CD117, an immunohistochemical marker that binds the KIT receptor, has shown an association with response to imatinib in gastrointestinal stromal tumors. Sporadic case reports of a partial response of DFSP to this tyrosine kinase inhibitor, led to evaluation of CD117 staining in these tumors, but the absence of staining suggests that adjuvant treatment with this drug should not be based on immunohistochemical assessment with CD117.…”

Dermatofibrosarcoma protuberans in a 10-year-old child

“…But there are difficult cases where molecular biology techniques support confirmation of diagnosis. 4,5 Other CD34-positive neoplasias include epitheloid sarcoma, spindle cell lipoma, CD34-positive cellular digital fibromas, and solitary fibrous tumors. 6,7 It has been speculated that DFSP derives from a subtype of nestin-immunoreactive mesenchymal stem cell that is different from the nestin-and SOX2-positive cell population of the perifollicular mesenchyme.…”