Release of circulating tumor cells and cell-free nucleic acids is an infrequent event in synovial sarcoma: liquid biopsy analysis of 15 patients diagnosed with synovial sarcoma

Abstract

BackgroundSynovial sarcoma is a rare soft tissue tumor which contains the unique SS18-SSX1, SS18-SSX2 – or, rarely, SS18-SSX4 - fusion transcripts. It is well known that some soft tissue tumors, like Ewing sarcomas and myxoid liposarcomas, can spread via the blood with free circulating tumor cells (CTC); this can be detected by several sensitive molecular biology methods. Here we report a study of fifteen synovial sarcoma patients with varied clinical backgrounds.MethodAfter blood withdrawal and nucleic acid isolation, we attempted to detect the SS18-SSX fusion genes from circulating tumor cells or cell-free nucleic acids with nested PCR and droplet digital PCR.ResultsSS18-SSX2 fusion transcript was identified in a small copy number with droplet digital PCR in one case. Nested PCR could not detect any of the fusion transcripts in the examined 15 synovial sarcoma cases.ConclusionsHeretofore two case reports could detect CTCs in synovial sarcoma - in the first paper, the patient was diagnosed with poorly differentiated type while the other had a rare primary gastric synovial sarcoma. However, until now, no other studies have detected CTCs in the peripheral blood of synovial sarcoma patients. Based on our findings, we can conclude that detection of the chimeric SS18-SSX fusion gene after surgical excision and/or chemotherapy/radiotherapy is a rare circumstance and hence in itself is not sufficient for monitoring the tumor recurrence. Therefore, monitoring of other possible biomarkers - for example synovial sarcoma specific miRNAs - is recommended.

Detection of SS18-SSX1/2 fusion transcripts in circulating tumor cells of patients with synovial sarcoma

“…The authors reported the presence of SS18-SSX2 fusion transcript in circulation of 1 of 15 patients (6.7%), which suggests that the presence of tumor-derived cell-free RNA or circulating tumors cells (CTCs) is a rare event in patients with synovial sarcoma. We performed a study in an independent cohort of 38 patients with synovial sarcoma and our results support the findings of Mihály et al [ 1 ].…”

“…We have read with great interest the study on release of circulating tumor cells and cell-free nucleic acids in synovial sarcoma by Mihály et al published in Diagnostic Pathology [ 1 ]. The authors reported the presence of SS18-SSX2 fusion transcript in circulation of 1 of 15 patients (6.7%), which suggests that the presence of tumor-derived cell-free RNA or circulating tumors cells (CTCs) is a rare event in patients with synovial sarcoma.…”

Sarcoma treatment in the era of molecular medicine

“…Despite the absence of specific markers, various methods of cell isolation based on physical specificity (e.g., higher size and higher cell deformability of tumor cells) or biological properties (e.g., immunomagnetic isolation) have been proposed with success (Gabriel et al , 2016; Hayashi et al , 2017; Li et al , 2017). CTCs are detectable in bone sarcomas (Chinen et al , 2014; Benini et al , 2018) and STS patients (Braun et al , 2018; Mihály et al , 2018; Przybyl et al , 2019). To improve the sensitivity and specificity of detection and isolation of CTCs across sarcoma subtypes, investigators have been looking for universal sarcoma markers (Satelli et al , 2014; Li et al , 2018).…”

The new horizon of liquid biopsy in sarcoma: the potential utility of circulating tumor nucleic acids

“…Synovial sarcoma(SS) is an aggressive soft tissue malignancy which characterized by the formation of the SYT-SSX fusion gene. Several researchers have attempted to validate the potential use of the circulating SYT-SSX fusion gene as a non-invasive biomarker in SS patients 65 , 150 - 152 . In 2001, Hashimoto et al detected the SYT-SSX fusion gene in peripheral blood by nested PCR in an SS patient 150 .…”

“…Based on these findings, subsequent studies investigated the potential of the circulating SYT-SSX fusion gene in liquid biopsy of SS patients. However, existing evidence revealed that the presence of the circulating SYT-SSX fusion gene was an infrequent event in SS patients and that the circulating SYT-SSX fusion gene was not an ideal marker to monitor tumor dynamics [65,152,153]. Therefore, the SYT-SSX fusion gene may not be a reliable circulating biomarker and further research is needed in SS patients.…”