TOP2A Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma
Jui Lan, Chien-Feng Li, Tzu-Ju Chen, Hui-Chun Tai, Hsuan-Ying Huang. Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chi-Mei Medical Center, Tainan, Taiwan; Southern Taiwan University of Science and Technology, Tainan, Taiwan; National Health Research Institutes, Tainan, Taiwan; Changhua Christian Hospital, Changhua, Taiwan
Background: 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, TOP2A was first identified as a differentially upregulated gene in NPC tissues, which encodes topoisomerase 2 alpha implicating cell division via selective cleavage, rearrangement, and re-ligation of DNA strands. Given the roles of TOP2A in prognostication and as the frontline therapeutic target in common carcinomas, such as breast cancer, we explored the significance of TOP2A immunoexpression status in a well-defined cohort of NPC patients.
Design: 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 results were correlated with the clinicopathological variables, disease-specific survival (DSS), and distant metastasis-free survival (DMFS).
Results: TOP2A overexpression was significantly associated with AJCC stages III-IV (p=0.019) and univariately predictive of adverse outcomes for DSS (p=0.0078) and DMFS (p=0.0003). In multivariate comparisons, TOP2A overexpression still 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.
Conclusions: 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.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 210, Wednesday Morning