Esmeralda Castelblanco1,2,3, Carles Zafon2,3,4, Javier Maravall3,5, Pilar Gallel6, Montserrat Martinez7, Ismael Capel3,8, Maria Rosa Bella3,9, Irene Halperin3,10, Jordi Temprana3,11, Carmela Iglesias3,11, Manel Puig-Domingo1,2,3, Mercedes Robledo12,13, Xavier Matias-Guiu6, Didac Mauricio1,2,3. 1. 1 Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol , Badalona, Spain . 2. 2 Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM) , ISCIII, Badalona, Spain . 3. 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain . 4. 4 Diabetes and Metabolism Research Unit (VHIR) and Department of Endocrinology, University Hospital Vall d'Hebron and Autonomous University of Barcelona , Barcelona, Spain . 5. 5 Department of Endocrinology and Nutrition, University Hospital Arnau de Vilanova and University of Lleida , Biomedical Research Institute of Lleida, Lleida, Spain . 6. 6 Department of Pathology and Molecular Genetics, University Hospital Arnau de Vilanova and University of Lleida , Biomedical Research Institute of Lleida, Lleida, Spain . 7. 7 Biostatistics and Epidemiology Unit, Biomedical Research Institute of Lleida , Lleida, Spain . 8. 8 Department of Endocrinology and Nutrition, University Hospital Parc Taulí Sabadell , Barcelona, Spain . 9. 9 Department of Pathology, University Hospital Parc Taulí Sabadell , Barcelona, Spain . 10. 10 Department of Endocrinology and Nutrition, University Hospital Clinic Barcelona , Barcelona, Spain . 11. 11 Department of Pathology, Vall d'Hebron University Hospital and Autonomous University of Barcelona , Barcelona, Spain . 12. 12 Hereditary Endocrine Cancer Group, Spanish National Cancer Centre , Madrid, Spain . 13. 13 Centre for Biomedical Research on Rare Diseases (CIBERER) , ISCIII, Madrid, Spain .
Abstract
BACKGROUND: Current methods based on fine-needle aspiration biopsy (FNAB) are not sufficient to distinguish among follicular thyroid lesions, follicular adenoma (FA), follicular thyroid carcinoma (FTC), and the follicular variant of papillary thyroid cancer (FVPTC). Furthermore, none of the immunohistochemical markers currently available are sensitive or specific enough to be used in the clinical setting, necessitating a diagnostic hemithyroidectomy. The aim of this study was to identify proteins of value for differential diagnosis between benign and malignant thyroid follicular lesions. METHODS: This retrospective analysis is based on an assessment of the immunoexpression of 19 proteins on 81 benign thyroid lesions (FA) and 50 malignant tumors (FTC/FVPTC). The resulting expression profile allowed the design of a scoring system model to improve the differential diagnosis of benign and malignant thyroid lesions. The model was validated using an independent series of 69 FA and 40 FTC and an external series of 40 nodular hyperplasias, and was further tested in a series of 38 FNAB cell blocks. RESULTS: A model based on the nuclear and cytoplasmic expression of APLP2, RRM2, and PRC1 discriminated between benign and malignant lesions with 100% sensitivity in both main and validation groups, with specificities of 71.3% and 50.7%, respectively. For the nodular hyperplasia series, specificity reached 94.8%. Finally, in FNAB samples, the sensitivity was 100% and the specificity was 45% for discrimination between benign and malignant lesions. CONCLUSIONS: These findings suggest that the identified APLP2, RRM2, and PRC1 signature could be useful for distinguishing between benign (FA) and malignant (FTC and FVPTC) tumors of the thyroid follicular epithelium.
BACKGROUND: Current methods based on fine-needle aspiration biopsy (FNAB) are not sufficient to distinguish among follicular thyroid lesions, follicular adenoma (FA), follicular thyroid carcinoma (FTC), and the follicular variant of papillary thyroid cancer (FVPTC). Furthermore, none of the immunohistochemical markers currently available are sensitive or specific enough to be used in the clinical setting, necessitating a diagnostic hemithyroidectomy. The aim of this study was to identify proteins of value for differential diagnosis between benign and malignant thyroid follicular lesions. METHODS: This retrospective analysis is based on an assessment of the immunoexpression of 19 proteins on 81 benign thyroid lesions (FA) and 50 malignant tumors (FTC/FVPTC). The resulting expression profile allowed the design of a scoring system model to improve the differential diagnosis of benign and malignant thyroid lesions. The model was validated using an independent series of 69 FA and 40 FTC and an external series of 40 nodular hyperplasias, and was further tested in a series of 38 FNAB cell blocks. RESULTS: A model based on the nuclear and cytoplasmic expression of APLP2, RRM2, and PRC1 discriminated between benign and malignant lesions with 100% sensitivity in both main and validation groups, with specificities of 71.3% and 50.7%, respectively. For the nodular hyperplasia series, specificity reached 94.8%. Finally, in FNAB samples, the sensitivity was 100% and the specificity was 45% for discrimination between benign and malignant lesions. CONCLUSIONS: These findings suggest that the identified APLP2, RRM2, and PRC1 signature could be useful for distinguishing between benign (FA) and malignant (FTC and FVPTC) tumors of the thyroid follicular epithelium.