Immunohistochemical Discrimination Between the ASPL-TFE3 Fusion Proteins of Alveolar Soft Part Sarcoma

Abstract

Summary: Alveolar soft part sarcoma (ASPS), a rare soft tissue sarcoma, is characterized by a chromosomal translocation der(17)t(X;17)(p11;q25) resulting in the production of 2 fusion proteins encoded by regions of the genes for alveolar soft part locus (ASPL) and the transcription factor E3 (TFE3). In this study, polyclonal antibodies were generated to 25 mer peptides encompassing the junctional regions of ASPL-TFE3 type 1 and ASPL-TFE3 type 2. The specificity of the affinity purified antibodies for the synthetic peptides and recombinant expressed ASPL-TFE3 type 1 and ASPL-TFE3 type 2 proteins was evaluated by enzyme-linked immunosorbent assay and was highly fusion type specific. Immunohistochemical staining of formalin-fixed, paraffin-embedded ASPS tumors with the fusion-specific antibodies resulted in intense nuclear staining and differentiation between tumors that express the type 1 protein and tumors that express the type 2 protein. These antibodies will be useful for the differential diagnosis of type 1 and type 2 ASPS and also in the detection of the fusion proteins in biochemical and cell biologic investigations.

Expression of MET in alveolar soft part sarcoma

“…It remains unclear whether different biologic significances are associated with the two ASPL-TFE3 fusions. Both type 1 and 2 ASPS tumors exhibited intense nuclear staining with an antibody against a C-terminal portion of TFE3, which is present in both types [16]. As previously reported, all of the ASPS tumors showed nuclear reactivity to TFE3 in our series.…”

Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

“…There are both FISH detection kits (Vysis, Abbot Laboratories, Abbott Park, IL) and specific monoclonal antibodies to detect the fusion protein generated by the rearrangement. 28 Figure 8 shows a CellSearch image gallery for CECs from an ASPS patient labelled with the monoclonal antibodies to the fusion protein, demonstrating the capture and identification of CTCs derived from ASPS and suggesting expanded uses for the CellSearch technology. To this end, we are currently testing a next generation CellSearch system that allows this positive tumor marker antibody phenotyping approach to be combined with a labelled antibody for evaluating a PD biomarker such as γH2AX (via the addition of a fifth analysis channel) to expand CTC PD measurements to a greater variety of patient populations.…”

Alveolar soft part sarcoma presenting with cutaneous metastases: Report of a case with immunohistochemical and molecular characterization

“…This antibody has been proven to be highly specific and sensitive for ASPS, but a subset of renal cell carcinomas developing in young people, some granular cell tumors, and perivascular epithelioid cell neoplasms can also express TFE3. 13,14 Recently, specific antibodies to differentiate type 1 and type 2 ASPL-TFE3 fusions have been developed, 15 and it has been shown that ASPS may have indistinctly both ASPL-TFE3 fusion types. In our case, the molecular study disclosed a type 2 ASPL-TFE3 fusion, but whether the biologic or clinical implications have a determined fusion type is still unknown.…”

“…In our case, the molecular study disclosed a type 2 ASPL-TFE3 fusion, but whether the biologic or clinical implications have a determined fusion type is still unknown. 15 The histologic differential diagnosis of metastasis of ASPS in the skin includes primary neoplasms composed of large polygonal and eosinophilic or clear cytoplasm, including common entities such as melanocytic tumors, granular cell tumor, appendageal neoplasms, and rare tumors such as paraganglioma and perivascular epithelioid cell neoplasms. [16][17][18][19][20][21][22] Moreover, metastasis of renal cell carcinoma may closely resemble ASPS.…”