title: APLP2, RRM2, and PRC1: New Putative Markers for the Differential Diagnosis of Thyroid Follicular Lesions.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: 1 Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol , Badalona, Spain .|2 Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM) , ISCIII, Badalona, Spain .|3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .
authors: Esmeralda
authors: E
authors: Castelblanco
authors: 2 Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM) , ISCIII, Badalona, Spain .|3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|4 Diabetes and Metabolism Research Unit (VHIR) and Department of Endocrinology, University Hospital Vall d'Hebron and Autonomous University of Barcelona , Barcelona, Spain .
authors: Carles
authors: C
authors: Zafon
authors: 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|5 Department of Endocrinology and Nutrition, University Hospital Arnau de Vilanova and University of Lleida , Biomedical Research Institute of Lleida, Lleida, Spain .
authors: Javier
authors: J
authors: Maravall
authors: 6 Department of Pathology and Molecular Genetics, University Hospital Arnau de Vilanova and University of Lleida , Biomedical Research Institute of Lleida, Lleida, Spain .
authors: Pilar
authors: P
authors: Gallel
authors: 7 Biostatistics and Epidemiology Unit, Biomedical Research Institute of Lleida , Lleida, Spain .
authors: Montserrat
authors: M
authors: Martinez
authors: 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|8 Department of Endocrinology and Nutrition, University Hospital Parc Taulí Sabadell , Barcelona, Spain .
authors: Ismael
authors: I
authors: Capel
authors: 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|9 Department of Pathology, University Hospital Parc Taulí Sabadell , Barcelona, Spain .
authors: Maria Rosa
authors: MR
authors: Bella
authors: 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|10 Department of Endocrinology and Nutrition, University Hospital Clinic Barcelona , Barcelona, Spain .
authors: Irene
authors: I
authors: Halperin
authors: 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|11 Department of Pathology, Vall d'Hebron University Hospital and Autonomous University of Barcelona , Barcelona, Spain .
authors: Jordi
authors: J
authors: Temprana
authors: 3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .|11 Department of Pathology, Vall d'Hebron University Hospital and Autonomous University of Barcelona , Barcelona, Spain .
authors: Carmela
authors: C
authors: Iglesias
authors: 1 Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol , Badalona, Spain .|2 Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM) , ISCIII, Badalona, Spain .|3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .
authors: Manel
authors: M
authors: Puig-Domingo
authors: 12 Hereditary Endocrine Cancer Group, Spanish National Cancer Centre , Madrid, Spain .|13 Centre for Biomedical Research on Rare Diseases (CIBERER) , ISCIII, Madrid, Spain .
authors: Mercedes
authors: M
authors: Robledo
authors: 6 Department of Pathology and Molecular Genetics, University Hospital Arnau de Vilanova and University of Lleida , Biomedical Research Institute of Lleida, Lleida, Spain .
authors: Xavier
authors: X
authors: Matias-Guiu
authors: 1 Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol , Badalona, Spain .|2 Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM) , ISCIII, Badalona, Spain .|3 Consortium for the study of thyroid cancer (CECaT) , Badalona, Spain .
authors: Didac
authors: D
authors: Mauricio
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C116662:PRC1 protein, human; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase
keywords: follicular adenoma; follicular thyroid cancer; follicular variant papillary thyroid carcinoma; immunohistochemistry; tissue microarray