title: The association between circulating tumor cells and Epstein-Barr virus activation in patients with nasopharyngeal carcinoma.
abstract: BACKGROUND
  Circulating tumor cells (CTCs) and microemboli (CTM) are attracting increasing attention in medical biology and clinical practice. However, the clinical relevance of CTCs in nasopharyngeal carcinoma (NPC) has not yet been ascertained, and no study has focused on the influence of Epstein-Barr virus (EBV) status on CTCs in NPC patients. These issues were therefore examined.
  
  
  METHODS
  Peripheral blood samples were prospectively obtained from 33 NPC patients before treatment. CTCs and CTM were captured using the Isolation by Size of Epithelial Tumor (ISET) method. Immunohistochemistry on CK5/6 (cytokeratin5/6) and P63, as well as in situ hybridization of EBERs (EBV-encoded RNAs) were used to validate the harvested tumor cells.
  
  
  RESULTS
  Out of 33 NPC patients, CTCs were detected in 22 cases (66.7%), and CTM were observed in 2 cases (6.1%). CTCs were presented in all stages of NPC patients but had no association with the TNM stages (all P > 0.05). The presence of CTCs appeared to correlate with EBV activation status. Among the total NPC patients, the EBV VCA-IgA levels in CTC-positive cases were higher than that in CTC-negative cases (negative vs. positive: 3.88 vs. 4.86, P = 0.016). A similar result was observed in the patients without distant metastasis (negative vs. positive: 3.76 vs. 4.95, P = 0.009). When the number of CTCs was considered, CTC counts were found to correlate with EBV VCA-IgA (R = 0.382, P = 0.041) and EBV DNA load (R = 0.396, P = 0.033) for all NPC patients as well as NPC patients without distant metastases.
  
  
  CONCLUSIONS
  These findings strongly suggested detectable CTCs/CTM in all stages of NPC patients and support a positive correlation between CTCs and EBV activation in NPC patients.
authors.affiliation: a Department of Molecular Diagnostics , Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: He
authors.affiliation: b Department of Nasopharyngeal Carcinoma Sun Yat-Sen University Cancer Center , State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Huang
authors.affiliation: c Department of Head and Neck of Sun Yat-sen University Cancer Center ; State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Su
authors.affiliation: a Department of Molecular Diagnostics , Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.affiliation: a Department of Molecular Diagnostics , Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Department of Molecular Diagnostics , Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Jiangjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: b Department of Nasopharyngeal Carcinoma Sun Yat-Sen University Cancer Center , State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: b Department of Nasopharyngeal Carcinoma Sun Yat-Sen University Cancer Center , State Key Laboratory of Oncology in South China , China ; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
mesh_terms: D000956:Antigens, Viral / Q000235:genetics* / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen
keywords: Circulating tumor cells (CTCs); epstein-Barr virus (EBV); nasopharyngeal carcinoma (NPC)