Abstract
Simple SummarySoft 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.
Highlights
We evaluated the expression of 5T4 in different histological subtypes of soft tissue sarcomas by immunohistochemical staining of tumor tissue microarrays (TMAs), and we confirm that it is widely expressed in STS
5T4 immunostaining in synovial sarcomas are presented to illustrate how the semi-quantitative immune-scoring method relates to immunostainto immune-scoring method relates to immunostaining toillustrate illustratehow howthe thesemi-quantitative semi-quantitative immune-scoring method relates to immunostaining seen seen intissues
Using immunohistochemical staining and a semi-quantitative scoring method, the expression of the glycoprotein 5T4 was evaluated in tissue microarrays containing cores of several histological subtypes of soft tissue sarcoma (STS)
Summary
Soft tissue sarcomas (STS) comprise a heterogeneous group of hard-to-treat malignancies originating from mesenchymal or connective tissues. They account for about 1% of cancers in adults [1] and 15% of cancers in children. In patients under 20 years old, STS is among the top five causes of cancer deaths in the United States [2,3]. The 5-year survival of STS on average is about 65% but ranges from 15% to about 80% depending on the tumor type, tumor grade at diagnosis, whether the cancer has metastasized, and whether a patient underwent surgery or not [5,6].
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