Abstract
BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionsThis 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.
Highlights
The preoperative characterization of thyroid nodules is a challenge for the clinicians
The decrease in helicase-like transcription factor (HLTF) staining was statistically significant during thyroid tumor progression in terms of both mean optical density (MOD), which corresponds to the mean staining intensity (KruskallWallis: p < 0.0005, Figure 3A), and the labelling index (LI), which corresponds to the percentage of immunopositive cells (Kruskall-Wallis: p < 10−6, Figure 3B)
Using a post-hoc comparison for pairs of groups, we observed that HLTF expression decreased when comparing adenomas to anaplastic carcinomas (MOD: p = 0.03, Figure 3A; LI: p = 0.05, Figure 3B), adenomas to follicular carcinomas (LI: p = 0.02, Figure 3B), papillary carcinomas to follicular carcinomas (MOD: p = 0.02, Figure 2A; LI: p = 0.000003, Figure 2B) and papillary carcinomas to anaplastic carcinomas (MOD: p = 0.002, Figure 3A; LI: p = 0.00006, Figure 3B)
Summary
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. There is an urgent need to identify biomarkers that could be used with the FNA to distinguish benign thyroid nodules from malignant tumors. Fineneedle aspiration (FNA) was the most commonly used pre-operative technique for diagnosis of a malignant thyroid tumor. There is an urgent need to identify new biomarkers that could be used in conjunction with the FNA to distinguish benign thyroid nodules from malignant tumors. Such biomarkers may provide crucial knowledge about the biology of well-differentiated thyroid cancers and, most likely, new directions for targeted therapies
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