Induction of epithelial-mesenchymal transition in thyroid follicular cells is associated with cell adhesion alterations and low-dose hyper-radiosensitivity.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with altered cellular adhesion. We previously demonstrated that cellular adhesion influences Low-dose Hyper-Radiosensitivity (HRS) in a variety of tumor cells. However, the relationship of low-dose HRS with the phenotypic plasticity incurred by EMT during the neoplastic transformation remains to be elucidated. OBJECTIVE: To investigate whether acquisition of EMT phenotype during progressive neoplastic transformation may affect low-dose radiation sensitivity. METHODS: Primary thyroid cells obtained from a human cystic thyroid nodule were first subjected to nutritional stress. This yielded immortalized INM-Thy1 cell strain, which was further treated with either multiple γ-radiation fractions (1.5 Gy each) or repetitive cycles of 3-methylcholanthrene and phorbol-12-myristate-13-acetate, yielding two progressive transformants, viz., INM-Thy1R and INM-Thy1C. Morphological alterations, chromosomal double-minutes, cell adhesion proteins, anchorage dependency, tumorigenicity in nude mice and cellular radiosensitivity were studied in these strains. RESULTS: Both transformants (INM-Thy1R, INM-Thy1C) displayed progressive tumorigenic features, viz., soft agar colony growth and solid tumor growth in nude mice, coupled with features of epithelial-mesenchymal transition and activated Wnt pathway. Incidentally, the chemical-induced transformant (INM-Thy1C) displayed a prominent HRS (αs/αr = 29.35) which remained unaffected at high cell density. However, the parental (INM-Thy1) cell line as well as radiation-induced transformant (INM-Thy1R) failed to show this hypersensitivity. CONCLUSION: The study shows that induction of EMT in thyroid follicular cells may accompany increased susceptibility to low-dose ionizing radiation, which was attenuated by adaptive resistance acquired during radiation-induced transformation.

Prospective evaluation of solitary thyroid nodule on 18F-FDG PET/CT and high-resolution ultrasonography.

PURPOSE: The utility of 18F-FDG PET/CT in the assessment of thyroid nodules is unclear as there are several conflicting reports on the usefulness of SUV as an indicator to distinguish benign from malignant thyroid lesions. This study incorporated an additional parameter, namely dual time point imaging, to determine the diagnostic accuracy of PET/CT imaging. The performance of 18F-FDG PET/CT was compared to that of high-resolution ultrasound which is routinely used for the evaluation of thyroid nodules. METHODS: Two hundred patients with incidentally detected solitary thyroid nodules were included in the study. Each patient underwent ultrasound and PET/CT evaluation within 7 days of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively, in a blinded manner. The PET/CT criteria employed were maximum SUV (SUV(max)) at 60 min and change in SUV(max) at delayed (120 min) imaging. Final diagnosis was based on pathological evaluation and follow-up. RESULTS: Of the 200 patients, 26 had malignant and 174 had benign nodules. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasound were 80.8, 81.6, 39.6, 96.6 and 81.5%, respectively. Using SUV(max) at 60 min as the diagnostic criterion, the above indices were 80.8, 84.5, 43.8, 96.7 and 84%, respectively, for PET/CT. The SUV(max) of malignant thyroid lesions was significantly higher than benign lesions (16.2 +/- 10.6 vs. 4.5 +/- 3.1, respectively; p = 0.0001). Incorporation of percentage change in SUV(max) at delayed imaging as the diagnostic criterion yielded a slightly improved sensitivity, specificity, PPV, NPV and accuracy of 84.6, 85.6, 46.8, 97.4 and 85.5%, respectively. There was a significant difference in percentage change in SUV(max) between malignant and benign thyroid lesions (14.9 +/- 11.4 vs. -1.6 +/- 13.7, respectively; p = 0.0001). However, there was no statistically significant difference (95% confidence interval) between the diagnostic performance of PET/CT and ultrasound. CONCLUSIONS: Routine use of 18F-FDG PET/CT with SUV(max) at 60 min as the sole diagnostic criterion does not appear to have a significant advantage over high-resolution ultrasound in the evaluation of thyroid nodules. Incorporation of dual time point imaging enhances image interpretation, and yields a higher diagnostic performance, yet it is not statistically significant. Bearing in mind the cost, limited availability and radiation exposure, routine use of 18F-FDG PET/CT for distinguishing benign from malignant thyroid nodules cannot be recommended.