title: Helicase-like transcription factor: a new marker of well-differentiated thyroid cancers.
abstract: BACKGROUND
  The preoperative characterization of thyroid nodules is a challenge for the clinicians. Fine-needle aspiration (FNA) is the commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. There is an urgent need to identify biomarkers that could be used with the FNA to distinguish benign thyroid nodules from malignant tumors. The purpose of the study is to examine the level of expression of the helicase-like transcription factor (HLTF) in relation to neoplastic progression of thyroid carcinomas.
  
  
  METHODS
  The presence of HLTF was investigated using quantitative and semi-quantitative immunohistochemistry in a series of 149 thyroid lesion specimens. Our first clinical series was composed of 80 patients, including 20 patients presenting thyroid adenoma, 40 patients presenting thyroid papillary carcinoma, 12 patients presenting thyroid follicular carcinoma and 8 patients presenting anaplastic carcinoma. These specimens were assessed quantitatively using computer assisted microscopy. Our initial results were validated on a second clinical series composed of 40 benign thyroid lesions and 29 malignant thyroid lesions using a semi-quantitative approach. Finally, the HLTF protein expression was investigated by Western blotting in four thyroid cancer cell lines.
  
  
  RESULTS
  The decrease of HLTF staining was statistically significant during thyroid tumor progression in terms of both the percentage of mean optical density (MOD), which corresponds to the mean staining intensity (Kruskall-Wallis: p < 0.0005), and the labelling index (LI), which corresponds to the percentage of immunopositive cells (Kruskall-Wallis: p < 10-6). Adenomas presented very pronounced nuclear HLTF immunostaining, whereas papillary carcinomas exhibited HLTF only in the cytoplasm. The number of HLTF positive nuclei was clearly higher in the adenomas group (30%) than in the papillary carcinomas group (5%).The 115-kDa full size HLTF protein was immunodetected in four studied thyroid cancer cell lines. Moreover, three truncated HLTF forms (95-kDa, 80-kDa and 70-kDa) were also found in these tumor cells.
  
  
  CONCLUSIONS
  This study reveals an association between HLTF expression level and thyroid neoplastic progression. Nuclear HLTF immunostaining could be used with FNA in an attempt to better distinguish benign thyroid nodules from malignant tumors.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Arcolia
authors.forename: Paula
authors.initials: P
authors.lastname: Paci
authors.forename: Ludovic
authors.initials: L
authors.lastname: Dhont
authors.forename: Gilbert
authors.initials: G
authors.lastname: Chantrain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirtaine
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Myriam
authors.initials: M
authors.lastname: Remmelink
authors.forename: Alexandra
authors.initials: A
authors.lastname: Belayew
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium. sven.saussez@umons.ac.be.
authors.forename: Sven
authors.initials: S
authors.lastname: Saussez
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000201:enzymology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000201:enzymology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D020033:Protein Isoforms; D014157:Transcription Factors