Abstract
Abstract Background: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinical significance in patients with metastatic clear cell RCCs (ccRCCs). Methods: We analyzed 206 metastatic ccRCC patients who received the first-line vascular endothelial growth factor (VEGF) targeted therapy including sunitinib (n = 33), pazopanib (n = 120), and sorafenib (n = 53) between 2006 and 2016. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to membranous staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). Results: TG2 staining intensity was negative in 20.9% of ccRCC (n = 43), 1+ in 46.6% (n = 96), 2+ in 9.71% (n = 20), and 3+ in 22.8% (n = 47). The survival analysis showed a significant association between stronger TG2 expression (≥ 2+) and worse progression-free survival (PFS) (P = 0.032) in the 1st line VEGF-targeted therapy. On multivariate analysis including previous nephrectomy, number of metastatic organs, and International Metastatic RCC Database Consortium Risk Score, stronger TG2 expression was a significant independent predictive indicator for poor PFS (P = 0.004). Conclusions: Our study is the first to demonstrate the significance of TG2 expression on clinical outcome in metastatic ccRCCs. TG2 expression was a significant negative predictive marker for PFS in 1st line VEGF-targeted therapy and targeting TG2 may be a new therapeutic approach to metastatic ccRCC. Citation Format: Seung-Hoon Beom, Sejung Park, Woo Sun Kwon, Sang Joon Shin, Soo-Youl Kim, Nam Hoon Cho, Sun Young Rha. Significance of Transglutaminase 2 expression on clinical outcome in metastatic renal cell carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A053. doi:10.1158/1535-7163.TARG-19-A053
Published Version
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