Ken Hatogai1,2,3, Satoshi Fujii4, Takashi Kojima2, Hiroyuki Daiko5, Shogo Nomura6, Toshihiko Doi2, Shigehisa Kitano7, Atsushi Ohtsu2, Yuichi Takiguchi3, Takayuki Yoshino2, Atsushi Ochiai1. 1. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 3. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan. 4. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. sfujii@east.ncc.go.jp. 5. Department of Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 6. Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Kashiwa, Chiba, Japan. 7. Department of Experimental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan.
Abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease in the sense that the biological behavior is regulated by the activation of various signaling pathways. The aim of this study was to investigate the relationships between the expressions of various targetable proteins and the clinicopathological characteristics of ESCC patients. METHODS: A total of 286 patients with ESCC who had undergone curative surgical resection without neoadjuvant therapy were enrolled in this study. The protein expressions of EGFR, HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were immunohistochemically evaluated in a tissue microarray analysis. The relationships between the expression statuses of each of the above molecules, and the PD-L1 expression status as well as the clinicopathological characteristics, including the survival outcome were assessed. RESULTS: The expression frequencies of EGFR, HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were as follows: 90.9, 1.0, 2.4, 71.0, 16.1, 62.9 and 23.4%. The overlapping expressions of two or more receptor tyrosine kinases were observed in 72.0%. MET expression was the only poor prognostic factor of recurrence-free survival [hazard ratio (HR) 1.89, 95% confidence interval (CI) 1.15-3.11]; in contrast, PD-L1 was the only favorable prognostic factor for both recurrence-free survival (HR 0.57, 95% CI 0.38-0.87) and overall survival (HR 0.56, 95% CI 0.35-0.89). No correlation was observed between the expressions of PD-L1 and the other molecules. CONCLUSIONS: This large cohort study demonstrated that multiple molecules were co-expressed in most of the ESCC cases, suggesting that combining molecular targeted agents for these co-expressed molecules should be considered.
BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease in the sense that the biological behavior is regulated by the activation of various signaling pathways. The aim of this study was to investigate the relationships between the expressions of various targetable proteins and the clinicopathological characteristics of ESCC patients. METHODS: A total of 286 patients with ESCC who had undergone curative surgical resection without neoadjuvant therapy were enrolled in this study. The protein expressions of EGFR, HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were immunohistochemically evaluated in a tissue microarray analysis. The relationships between the expression statuses of each of the above molecules, and the PD-L1 expression status as well as the clinicopathological characteristics, including the survival outcome were assessed. RESULTS: The expression frequencies of EGFR, HER2, MET, IGF1R, FGFR2, p53, and PD-L1 were as follows: 90.9, 1.0, 2.4, 71.0, 16.1, 62.9 and 23.4%. The overlapping expressions of two or more receptor tyrosine kinases were observed in 72.0%. MET expression was the only poor prognostic factor of recurrence-free survival [hazard ratio (HR) 1.89, 95% confidence interval (CI) 1.15-3.11]; in contrast, PD-L1 was the only favorable prognostic factor for both recurrence-free survival (HR 0.57, 95% CI 0.38-0.87) and overall survival (HR 0.56, 95% CI 0.35-0.89). No correlation was observed between the expressions of PD-L1 and the other molecules. CONCLUSIONS: This large cohort study demonstrated that multiple molecules were co-expressed in most of the ESCC cases, suggesting that combining molecular targeted agents for these co-expressed molecules should be considered.
Entities:
Keywords:
Esophageal cancer; PD-L1; Receptor tyrosine kinase; Squamous cell cancer
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