Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors

SIMPLE SUMMARY: Most of the immunohistochemical markers for gastrointestinal stromal tumor (GIST) are also expressed in other sarcomas relevant for the differential diagnosis of GIST, and thus, new immunohistochemical markers can be of help in GIST diagnostics. Tensin2 (TNS2) was found to be downregulated in most human cancers but overexpressed in GIST; we therefore investigated the role of TNS2 as a diagnostic biomarker for GIST. The results provide conclusive evidence for the value of TNS2 as a sensitive and specific diagnostic biomarker for GIST, with stronger associations for gastric and non-metastatic tumors. These findings can be of use in the differential diagnosis of GIST, especially while trying to differentiate other tumors of the stomach, such as lipo- and leiomyosarcomas, from GISTs. ABSTRACT: GIST is a rare soft tissue sarcoma, for which KIT and DOG1 are used as highly sensitive diagnostic markers. Other diagnostic markers include CD34, protein kinase C θ, deficiency of succinate dehydrogenase complex subunit B, carbonic anhydrase II, and type I insulin-like growth factor receptor. We investigated the role of TNS2 as a diagnostic biomarker by using immunohistochemistry in 176 GISTs and 521 other sarcomas. All GISTs expressed TNS2, with intermediate or high expression in 71.4% of samples. The majority (89.8%) of other sarcomas were negative for TNS2, and intermediate to strong staining was only seen in 2.9% of samples. Strong TNS2 staining was associated with gastric location (gastric 52.8% vs. non-gastric 7.2%; p < 0.001), absence of metastases (non-metastatic tumors 44.3% vs. metastatic tumors 5.9%; p = 0.004), female sex (female 45.9% vs. male 33.8%; p = 0.029), and tumors of lower risk categories (very low or low 46.9% vs. intermediate 51.7% vs. high 29.0%; p = 0.020). TNS2 expression did not correlate with overall survival or metastasis-free survival. No associations between TNS2 expression and KIT/PDGFRA mutation status, tumor size, mitotic count, or age of the patient were detected. The results provide conclusive evidence for the value of TNS2 as a sensitive and specific diagnostic biomarker for GIST.