title: Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas.
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.
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou City, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Xu
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Zheng
authors.forename: Zhi-Xuan
authors.initials: ZX
authors.lastname: Fu
authors.forename: Zhu-Peng
authors.initials: ZP
authors.lastname: Li
authors.forename: Hua-Xia
authors.initials: HX
authors.lastname: Xie
authors.forename: Xian-Xing
authors.initials: XX
authors.lastname: Li
authors.forename: Lie-Hao
authors.initials: LH
authors.lastname: Jiang
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shuang-Mei
authors.initials: SM
authors.lastname: Zhu
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II