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Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas

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Abstract

Topoisomerase 2α (Topo2A) is a key enzyme in replication. It functions as a cell proliferation and cell cycle-specific marker and it is identified mainly in the interphase nuclei of proliferating cells. Many studies have shown that Topo2A protein expression is up-regulated in various cancers including esophageal cancer. However, to date, no studies have adequately addressed the prognostic value of Topo2A in patients with resectable esophageal squamous cell carcinoma (ESCC). Therefore, we conducted a large-scale retrospective study investigating the expression of Topo2A and the clinicopathological characteristics or prognosis of ESCC patients. Eight hundred and twenty-nine specimens of ESCC from patients who underwent complete esophageal cancer resection were evaluated using an immunohistochemical assay. Among them, 404 (48.7 %) cases with a score >2 were determined to be positive for Topo2A expression. Topo2A overexpression was significantly associated with poorer differentiation (P = 0.007) and perineural invasion (P = 0.046). The median progression-free survival (PFS) of 319 patients with Topo2A-positive expression and 336 patients with Topo2A-negative expression was 19.5 and 26.5 months, respectively (P = 0.000). The overall survival (OS) in patients with and without Topo2A expression was 34.0 and 44.5 months, respectively (P = 0.002). In the multivariate analysis, Topo2A overexpression was identified as an independent prognostic factor for PFS (P = 0.001) and OS (P = 0.009). We determined that Topo2A overexpression was not only associated with poorer differentiation and perineural invasion, but it could also act as an independent risk factor for ESCC.

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Acknowledgments

This work was supported by the Province Important Technology and Science Program (Special Feature of Major Province Scientific and Technological Program 2011), No. 2011C13039-1, and the establishment and NSFC general Program, No. 81172081 and No. 81372210.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou City, China

    Xiao-Ling Xu & Hua-Xia Xie

  2. Key Laboratory on Diagnosis and Treatment Technology on Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute), Hangzhou, 310022, Zhejiang Province, China

    Xiao-Ling Xu, Wei-Hui Zheng, Zhu-Peng Li, Lie-Hao Jiang & Wei-Min Mao

  3. Department of Anal-Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang Province, China

    Zhi-Xuan Fu

  4. Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang Province, China

    Xian-Xing Li

  5. The Physical Examination Center, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, China

    Yin Wang

  6. Department of Radio-Chemotherapy Oncology, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Shuang-Mei Zhu

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  1. Xiao-Ling Xu
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Correspondence to Wei-Min Mao.

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Xu, XL., Zheng, WH., Fu, ZX. et al. Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas. Med Oncol 32, 396 (2015). https://doi.org/10.1007/s12032-014-0396-7

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