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 overlap** 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.
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Acknowledgements
We are grateful to Ms. Yuka Nakamura for technical assistance.
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The authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the institutional review board of the National Cancer Center (Registration No. 2014-135).
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Informed consent was obtained from all individual participants included in the study.
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Hatogai, K., Fujii, S., Kojima, T. et al. Large-scale comprehensive immunohistochemical biomarker analyses in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 143, 2351–2361 (2017). https://doi.org/10.1007/s00432-017-2482-7
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DOI: https://doi.org/10.1007/s00432-017-2482-7