Molecular analyses of cell origin and detection of circulating tumor cells in the peripheral blood in alveolar soft part sarcoma

Abstract

Alveolar soft part sarcoma (ASPS) is a distinct, rare soft tissue tumor with an unknown histogenesis and a tendency for late widespread metastases to lung, bone, and brain. It is now clear that they are caused by a specific unbalanced translocation, der(17)t(X;17)(p11;q25), which results in the formation of an ASPSCR1–TFE3 (alias ASPL–TFE3) fusion gene;. The rearrangement results in the expression of chimeric transcripts, which can be identified by means of reverse transcriptase–polymerase chain reaction (RT-PCR). We investigated the histogenesis of ASPS and attempted to detect circulating ASPS tumor cells in peripheral blood. The immunohistochemical and genetic details of four cases and one cell line of ASPS were examined. An immunohistochemical analysis and RT-PCR did not detect myogenic differentiation gene MYOD1. The sensitivity of nested RT-PCR for detection of circulating ASPS cells was assessed by demonstrating that the tumor cell–associated gene translocation could be detected in 50 tumor cells/2 mL of blood. Clinically, it was detectable in a peripheral blood sample (2 mL) of ASPS patient with distant metastases. The findings suggest that ASPS is not of skeletal muscle origin. ASPS tumor cells in the peripheral blood could be monitored by RT-PCR.