High Prevalence of 5T4/Trophoblast Glycoprotein in Soft Tissue Sarcomas

Simple Summary: Soft tissue sarcoma (STS) is a heterogeneous group of hard-to-treat malignancies from mesenchymal or connective tissues. The treatment options in case the cancer relapses after surgery or is at an advanced state are limited, and in all cases the response rates are low. Targeted therapy with antibody drug conjugates may provide an alternative. To this end, molecules that are specifically (over)expressed on the surface of the tumor cells are needed. In this study, we show that 5T4/trophoblast glycoprotein, a molecule with limited expression in healthy tissues, is prominently expressed on the cell surface of many STS subtypes and can be used for such an approach. The expression of 5T4/trophoblast glycoprotein was evaluated in several histological subtypes of soft tissue sarcoma (STS) to determine whether the prevalence and level of expression of this membrane-associated glycoprotein is sufficient for use in targeted therapies. Tumor tissue microarrays containing cores from different histological subtypes of STS were stained using a standardized immunohistochemical staining method to detect 5T4; the level of staining was assessed using a semi-quantitative scoring method. No 5T4 staining was seen in the angiosarcomas and liposarcomas investigated in this study. 5T4 staining in the other STS subtypes was seen in more than 50% of cases, warranting further investigation into whether this antigen could evoke an anti-tumor immune response or can be used as target for the delivery of more potent toxins through antibody drug conjugates.

Automated summary

Soft tissue sarcoma (STS) is a difficult-to-treat malignancy originating from mesenchymal or connective tissues. The molecule 5T4/trophoblast glycoprotein is found to be prominently expressed on the cell surface of many STS subtypes, making it a potential target for targeted therapies. Further investigation is warranted to determine whether this antigen could trigger an anti-tumor immune response or serve as a target for delivering more potent toxins through antibody drug conjugates, as it is expressed in more than 50% of other STS subtypes.