title: Diagnostic value of 16 cellular tumor markers for metastatic thyroid cancer: an immunohistochemical study.
abstract: BACKGROUND
  The prognosis for thyroid cancer differs between metastatic and non-metastatic cases. To identify biomarkers useful for thyroid cancer diagnosis and to establish a marker panel for the early detection of metastatic thyroid carcinoma, this study compared histomorphological features and biomarker expression profiles in thyroid carcinomas according to pathological diagnoses.
  
  
  METHODS
  Thyroid carcinoma samples were obtained from 113 consecutive patients who underwent resection at multiple centers between 2001 and 2008. These cases included 63 metastatic thyroid tumors (34 papillary carcinomas, 20 follicular carcinomas, 9 undifferentiated carcinomas) and 50 non-metastatic thyroid tumors (36 papillary carcinomas, 14 follicular carcinomas). Tissue microarrays constructed using the 113 samples were analyzed by immunohistochemistry for the expression of 16 protein markers: MMP9, VEGF-C, E-cadherin, MMP2, PPARγ, PCNA, CXCR4, PTEN, C-myc, PTTG, HBME-1, p16, p53, FHIT, bFGF and hTERT. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and the predictive values of the identified biomarkers for metastasis in thyroid carcinoma were determined by receiver operating characteristic (ROC) curve analysis.
  
  
  RESULTS
  The expression of six proteins, VEGF-C, MMP2, CXCR4, PTTG, HBME-1 and bFGF, was up-regulated in metastatic compared to non-metastatic thyroid carcinoma. Multiple factor binary ordinal logistic regression analysis showed that MMP2, PTTG, VEGF-C, CXCR4 and bFGF were independent factors associated with the metastatic status of thyroid carcinoma. ROC curve analysis of these five proteins revealed that VEGF-C and bFGF were the most useful protein markers for the diagnosis of metastatic thyroid cancer.
  
  
  CONCLUSIONS
  MMP2, PTTG, VEGF-C, CXCR4 and bFGF are potential cellular tumor markers for identifying thyroid cancer with greater risk for metastasis and the novel combination of VEGF-C and bFGF as biomarkers may improve the accuracy of early detection and the differential diagnosis between metastatic and non-metastatic thyroid carcinoma.
authors.affiliation: Beihai Institute of Endocrine and Metabolic Diseases, Ninth Affiliated Hospital of Guangxi Medical University, Beihai 536000, China. flowchaos@yahoo.com.cn
authors.forename: Huasheng
authors.initials: H
authors.lastname: Liang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhong
authors.forename: Zuojie
authors.initials: Z
authors.lastname: Luo
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Huade
authors.initials: H
authors.lastname: Lin
authors.forename: Song
authors.initials: S
authors.lastname: Zhan
authors.forename: Kaiqing
authors.initials: K
authors.lastname: Xie
authors.forename: Qingdi Quentin
authors.initials: QQ
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D011237:Predictive Value of Tests; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins