Helicase-like transcription factor: a new marker of well-differentiated thyroid cancers
- Equal contributors
1 Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium
2 Laboratory of Molecular Biology, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium
3 Department of Oto-Rhino-Laryngology, CHU Saint-Pierre, Free University of Brussels, Brussels, Belgium
4 Department of Pathology, Institute Bordet, Free University of Brussels, Brussels, Belgium
5 Laboratory of Image, Signal Processing and Acoustics (LISA), Ecole Polytechnique de Bruxelles, Free University of Brussels, Brussels, Belgium
6 Department of Pathology, Hospital Erasme, Free University of Brussels, Brussels, Belgium
7 Present address: Laboratory of Neurosciences, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons, 7000 Mons, Belgium
BMC Cancer 2014, 14:492 doi:10.1186/1471-2407-14-492Published: 8 July 2014
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.
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.
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.
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.