Introduction: Esophageal squamous cell carcinoma (ESCC), which is the most common type of esophageal cancer, is one of the most common cancers in eastern Asia and one of the leading causes of cancer-related death worldwide. This unsatisfactory outcome in ESCC is thought to mainly result from late diagnosis, the aggressiveness of this disease, and the lack of the understanding in effective treatment strategies. Therefore, new targetable drugs are required to be investigated and developed in order to improve treatment strategies. The discoidin domain receptors (DDRs) are a set of receptor tyrosine kinases (RTKs) that are activated by collagen and crucial role in key regulators in cancer progression by controlling the interactions of tumor cells with their surrounding collagens. DDR1 is expected to be involved in ESCC, which demonstrates aggressive tumor proliferation and devastating prognosis. However, there have been only a few reports about DDR1 in ESCC. We retrospectively investigated DDR1 in ESCC.

Methods: A total of 60 formalin-fixed paraffin-embedded (FFPE) primary tumor samples were collected from patients with ESCC who underwent surgery with curative intent. DDR1 immunohistochemistry (IHC) was conducted on ESCC FFPE tissue specimens. Clinicopathological factors, DDR1 immunohistochemistry (IHC) and survival data were analyzed in this study.

Results: When compared the clinicopathological factors between the weak and the strong group in the intensity of DDR1 IHC, in univariate analysis there were significant differences between the two groups in age (P=0.007), histological grade (P=0.04), invasion depth (P=0.0001), stage (P< 0.0001). There were no significant differences between the two groups with respect to the other clinicopathological factors. In univariate analysis, significant differences in recurrence-free survival were recognized with respect to invasion depth (T3, 4) (P=0.007), lymph node metastasis (LNM) (N2, 3) (P=0.0005) and DDR1 IHC expression (strong) (P=0.0009). When these clinicopathological factors were used as co-variables for the multivariate analysis, LNM and DDR1 IHC expression were found to be significantly independent prognostic factors (LNM; P=0.04, HR=4.20, DDR1; P=0.03, HR=4.27).

Conclusion: DDR1 IHC expression was found to be useful as a biomarker to predict long-term outcome.

Citation Format: Kiichi Sugimoto, Tomoaki Ito, Hajime Orita, Koichi Sato, Kazuhiro Sakamoto, Mutsumi Sakurada, Tomoyuki Kushida, Hiroshi Maekawa, Ellen Tully, Juhyung Woo, Edward Gabrielson. Discoidin domain receptor-1 (DDR1) is an independent prognostic marker of poor prognosis in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5928. doi:10.1158/1538-7445.AM2017-5928