title: Aberrant expression of TfR1/CD71 in thyroid carcinomas identifies a novel potential diagnostic marker and therapeutic target.
abstract: BACKGROUND
  Type I receptor for transferrin (TfR1/CD71) is overexpressed in several malignant tumors, but no studies are available on thyroid carcinomas. Our previous comparative analyses of the relative distribution of transferrin in benign versus papillary thyroid carcinoma (PTC) tissues highlighted a marked malignancy-associated abundance of the molecule. The aim of the present study was to evaluate whether TfR1/CD71 is also differentially expressed in benign versus malignant thyroid tissues.
  
  
  METHODS
  Tissue samples, including benign lesions and follicular-derived carcinomas, from 241 patients and a total of 35 benign and malignant fresh specimens were assayed for TfR1/CD71 expression by reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry.
  
  
  RESULTS
  We found that transcription of TfR1/CD71 gene is constitutive in thyroid epithelia, but the mRNA is differently translated in benign and malignant tissues. Western blot revealed higher levels of TfR1/CD71 protein in malignant versus benign tissues. Immunohistochemically, most carcinomas exhibited overexpression of the receptor, predominantly in the cytoplasm of neoplastic cells. The highest expression level was detected in primary and metastatic papillary carcinomas and anaplastic carcinomas, with positive results ranging from 86% to 100% of the cases. In contrast, most benign tissues were negative, with only a minority of cases showing focal and weak immunoreactivity.
  
  
  CONCLUSIONS
  Our findings suggest that altered expression of TfR1/CD71 may be used as a marker helpful in distinguishing PTC from papillary hyperplasia and follicular variant PTC from benign follicular-patterned lesions. Additionally, the present observations support the rationale for the use of radiolabeled transferrin/transferrin analogs and/or anti-TfR1/CD71 antibodies for diagnostic and/or radiotherapeutic purposes in TfR1/CD71-expressing thyroid tumors.
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele," Anatomic Pathology, University of Catania, Catania, Italy. g.magro@unict.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.forename: Ivana
authors.initials: I
authors.lastname: Cataldo
authors.forename: Paolo
authors.initials: P
authors.lastname: Amico
authors.forename: Antonietta
authors.initials: A
authors.lastname: Torrisi
authors.forename: Giada Maria
authors.initials: GM
authors.lastname: Vecchio
authors.forename: Rosalba
authors.initials: R
authors.lastname: Parenti
authors.forename: Sofia
authors.initials: S
authors.lastname: Asioli
authors.forename: Daniele
authors.initials: D
authors.lastname: Recupero
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Mucignat
authors.forename: Roberto
authors.initials: R
authors.lastname: Perris
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C068126:CD71 antigen; D012333:RNA, Messenger; D011990:Receptors, Transferrin