title: TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.
abstract: Despite the advances in diagnostic imaging and treatment modalities, the risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database, topoisomerase IIα (TOP2A) was first identified as a differentially upregulated gene in NPC tissues, which implicates cell division via selective cleavage, rearrangement, and re-ligation of DNA strands. Given the roles of TOP2A in prognostication and in the frontline therapeutic regimen of common carcinomas, such as breast cancer, we explored TOP2A immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. TOP2A immunohistochemistry was retrospectively performed and analyzed using H-score method for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring TOP2A overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS) and distant metastasis-free survival (DMFS). TOP2A overexpression was significantly associated with American Joint of Cancer Committee (AJCC) stages III-IV (p = 0.019) and univariately predictive of adverse outcomes for DSS (p = 0.0078) and DMFS (p = 0.0003). In the multivariate comparison, TOP2A overexpression remained prognostically independent to portend worse DSS (p = 0.047, hazard ratio = 1.732) and DMFS (p = 0.003, hazard ratio = 2.569), together with advanced AJCC stages III-IV. TOP2A expression is upregulated in a subset of NPCs and its increased immunoexpression significantly correlated with advanced stages and tumor aggressiveness, justifying the potentiality of TOP2A as a prognostic biomarker and a novel therapeutic target of NPC.
authors.affiliation: Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jui
authors.initials: J
authors.lastname: Lan
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Tzu-Ju
authors.initials: TJ
authors.lastname: Chen
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Tai
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Hsu
authors.forename: Kwang-Yu
authors.initials: KY
authors.lastname: Chang
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D002277:Carcinoma; D016000:Cluster Analysis; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human
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