Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Abstract

Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).

Figure 1

Examples of expression scores. (a) No expression (CEA), (b) low expression (PDGFRa), (c) moderate expression (VEGF), (d) strong expression (TEM1).

Figure 2

IRS Expression scores.

Figure 3

(a) H&E staining of MFS and adjacent fascia and muscle. (b) Corresponding TEM1 staining shows strong TEM1 expression in MFs and virtually no TEM1 expression in adjacent fascia and muscle. (c) H&E staining of a MFS bordering and muscle tissue. Infiltrative growth along fatty septa is clearly visible. (d) Corresponding TEM1 staining shows clear contrast between TEM1 expressing MFS and bordering muscular tissue. Microscopic tumor extensions in the septa show strong TEM1 expression. (e) H&E staining of a MFS growing into subcutaneous fat. (e) Corresponding TEM1 staining shows strong expression of TEM1 in MFS and clear contrast with TEM1 negative adjacent subcutaneous fat. ***Dashed lines indicate tumor borders, T = Tumor, Fs = Fascia, M = Muscle, Ft = Fat.