73P - TROP2 amplification is highly present in dedifferentiated liposarcoma: Data from the Cancer Genome Atlas (TCGA) in soft tissue sarcoma

Background

Trophoblast cell surface antigen 2 (TROP2), or tumor-associated calcium signal transducer 2 TACSTD2, is a transmembrane transducer of intracellular calcium signal involved in tumor cell proliferation. Sacituzumab-govitecan a TROP2-targeting antibody-drug conjugate (ADC), is approved for breast cancer. Implications of TROP2 amplification (amp) in soft tissue sarcoma (STS) are understudied.

Methods

Amp defined by either CNV (Affymetrix single nucleotide polymorphism [SNP] 6.0 array data) or transcriptome (RNA-Seq_v2, log2- transformed RNA-Seq by expectation maximization [RSEM] normalized values) via cBioPortal. Query for amp of “TACSTD2” gene showed 494 samples of STS in 3 cohorts: Sarcoma TCGA, PanCancer Atlas – Cohort1, Sarcoma (MSKCC/Broad, Nat Genet 2010)- Cohort2 and Pan-cancer analysis of whole genomes (ICGC/TCGA, Nature 2020) – Cohort3. For Cohort1, we extracted clinical data from TCGA Research Network; analysis of TCGA PanCancer Atlas with 2,922 pan-cancer cases was also evaluated.

Results

Cohort1 (253 patients) included dedifferentiated liposarcoma (DDLPS), myxofibrosarcoma (MFS), malignant peripheral nerve sheath tumor (MPNST), synovial sarcoma (SS), leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS). 7% (17/253) exhibited amp of TACSTD2/TROP2 glycoprotein. The DDLPS group included 59 samples, with 11 (19 %) patients with amp. DDLPS clinical data included: median age 62 years, 46 patients with retroperitoneum DDLPS, 20.5 cm median size. 22 patients had R0 surgery. For UPS, amp was observed in 3 cases (6%) of 50 patients. For 24 MFS cases, 4% had the amp. Although the cohort was enriched with LMS, only 2% presenting amp. Cohort2 (207 patients) included DDLPS (24.2%). 19 patients (9%) had amp. Cohort3 included 34 patients with either DDLPS or LMS. Of the cohort 9% presented with amp. 3 of 19 patients with DDLPS (16%). PanCancer Atlas consisted of 2,922 samples across 38 cancers. TROP2 amp detected in 32 samples (2 %). Liposarcoma exhibits the highest amp rate followed by bone cancer and breast cancer. These findings corroborate that patients with DDLPS are enriched for the amp.

Conclusions

Our results support prospective analysis of TROP2 amp in DDLPS clinical trials.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Pollack: Financial Interests, Personal, Invited Speaker: SpringWorks; Financial Interests, Personal, Advisory Board: Deciphera, Aadi. B. Vincenzi: Financial Interests, Personal, Invited Speaker: PharmaMar, Deciphera, Boehringer Ingelheim. P. Viveiros: Financial Interests, Personal, Invited Speaker: SpringWorks. All other authors have declared no conflicts of interest.