title: The new molecular markers DDIT3, STT3A, ARG2 and FAM129A are not useful in diagnosing thyroid follicular tumors.
abstract: Preoperative characterization of thyroid follicular lesions is challenging. Fine-needle aspiration specimens cannot differentiate follicular carcinomas from benign follicular neoplasias. Recently, promising markers have been detected using modern molecular techniques. We conducted a retrospective study to confirm the usefulness of immunohistochemical staining for the protein markers, DDIT3, STT3A (ITM1), ARG2 and FAM129A (C1orf24) in separating benign and malignant thyroid follicular lesions. Formalin-fixed, paraffin-embedded thyroid tissue from 30 in-house cases (15 follicular carcinomas and 15 follicular adenomas), as well as 8 follicular carcinomas and 21 follicular adenomas on tissue microarray slides were stained immunohistochemically for DDIT3, STT3A, ARG2 and FAM129A expression. Control tissue consisted of thyroid parenchyma adjacent to the tumors and 11 separate cases of normal thyroid parenchyma. All in-house cases of follicular adenomas, follicular carcinomas and adjacent normal thyroid tissue showed positive immunostaining with anti-DDIT3 and anti-STT3A. Anti-ARG2 and anti-FAM129A polyclonal antibodies showed positive staining in 20 and 60% of in-house follicular adenomas, and 40 and 87% of in-house follicular carcinomas, respectively. Monoclonal anti-FAM129A demonstrated positive staining in 13 and 33% of in-house follicular adenomas and follicular carcinomas, respectively. Polyclonal anti-DDIT3, -STT3A and -FAM129A antibodies showed positive staining in all tissue microarray slides of follicular carcinoma and in 76, 85 and 81% of the follicular adenomas, respectively. Monoclonal anti-STT3A stained 81% of the follicular adenoma cores. Anti-ARG2 stained positive in 13% of follicular carcinomas and 10% of follicular adenomas on the tissue microarray slides. In conclusion, DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma.
authors.affiliation: Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital HF, Montebello, Norway. ESP@ous-hf.no
authors.forename: Eva
authors.initials: E
authors.lastname: Sigstad
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paus
authors.forename: Trine
authors.initials: T
authors.lastname: Bjøro
authors.forename: Aasmund
authors.initials: A
authors.lastname: Berner
authors.forename: Krystyna Kotanska
authors.initials: KK
authors.lastname: Grøholt
authors.forename: Lars H
authors.initials: LH
authors.lastname: Jørgensen
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.forename: Ruth
authors.initials: R
authors.lastname: Holm
authors.forename: David J
authors.initials: DJ
authors.lastname: Warren
mesh_terms: D018263:Adenocarcinoma, Follicular; D000236:Adenoma / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D001119:Arginase / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D003937:Diagnosis, Differential; D006602:Hexosyltransferases / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D009664:Norway; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D046888:Tissue Array Analysis; D051742:Transcription Factor CHOP / Q000032:analysis*; D051017:Apoptosis Regulatory Proteins
chemical_list: D001119:Arginase; D014408:Biomarkers, Tumor; D006602:Hexosyltransferases; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051742:Transcription Factor CHOP; C497249:DDIT3 protein, human; C516108:NIBAN1 protein, human; D051017:Apoptosis Regulatory Proteins; C099573:STT3A protein, human