title: Prognostic significance of thyroglobulin antibody epitopes in differentiated thyroid cancer.
abstract: BACKGROUND
  Thyroglobulin antibodies (TgAbs) are surrogate markers of disease recurrence or persistence in differentiated thyroid cancer (DTC). However, the prognostic significance of TgAb heterogeneity in DTC has not been investigated.
  
  
  OBJECTIVE
  To evaluate the relationship between TgAb epitope specificities and clinical outcomes in DTC patients.
  
  
  METHODS
  We studied 61 TgAb-positive patients with DTC, post-thyroidectomy and remnant ablation (7 males, 54 females; age-range 16-80 years, median follow-up duration 8.9 years). TgAb epitope reactivities were mapped using a panel of 10 thyroglobulin (Tg) monoclonal antibodies delineating six antigenic Tg clusters in competitive ELISA studies. Sera from 45 patients with Hashimoto's thyroiditis (HT) and 22 TgAb-positive healthy subjects served as autoimmune and healthy controls. Tg was measured by immunoradiometric assay (IRMA), electrochemiluminescence immunoassay (ECLIA), and RIA, while TgAbs was measured by ELISA and ECLIA methods.
  
  
  RESULTS
  Samples from 26 DTC patients showed TgAb epitope restriction similar to HT patients, while 35 patients exhibited nonspecific reactivity comparable to healthy controls. DTC patients with epitope restriction had higher rates of recurrent/persistent disease (81% vs 17%, P < .001), higher median TgAb concentration (887.0 vs 82.0 kIU/L; P < .001), and a higher prevalence of thyroid lymphocytic infiltration (71.4% vs 26.8%; P < .001) compared to patients with nonspecific reactivity. Samples with epitope restriction also had a lower median Tg-IRMA/RIA ratio (3.0% vs 36.0%; P < .001) denoting greater degrees of Tg assay interference.
  
  
  CONCLUSIONS
  TgAb epitope restriction is associated with a less favorable prognosis than nonspecific reactivity in DTC patients. TgAb epitope specificities may have prognostic value in DTC.
authors.affiliation: Department of Clinical Medicine and Surgery (G.A.L., G.L.), University "Federico II," Via Pansini 5, 80131, Naples, Italy; Thyroid Research Group (O.E.O., L.D.K.E.P., J.H.L.), Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, CF14 4XN, United Kingdom; Department of Endocrinology and Diabetes (O.E.O.), Prince Charles Hospital, Cwm Taf Local Health Board, Merthyr Tydfil, Mid Glamorgan, CF47 9DT, United Kingdom; Department of Medical Biochemistry (C.E., A.J.P.), University Hospital Wales, Cardiff, CF14 4XN, United Kingdom; Clinical Laboratory Services (P.M.C.), Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, United Kingdom.
authors.forename: G A
authors.initials: GA
authors.lastname: Lupoli
authors.forename: O E
authors.initials: OE
authors.lastname: Okosieme
authors.forename: C
authors.initials: C
authors.lastname: Evans
authors.forename: P M
authors.initials: PM
authors.lastname: Clark
authors.forename: A J
authors.initials: AJ
authors.lastname: Pickett
authors.forename: L D K E
authors.initials: LD
authors.lastname: Premawardhana
authors.forename: G
authors.initials: G
authors.lastname: Lupoli
authors.forename: J H
authors.initials: JH
authors.lastname: Lazarus
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D000939:Epitopes; D005260:Female; D005500:Follow-Up Studies; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013954:Thyroglobulin / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D013954:Thyroglobulin