Aberrant Expression of TfR1/CD71 in Thyroid Carcinomas Identifies a Novel Potential Diagnostic Marker and Therapeutic Target

Type I receptor for transferrin (TfR1/CD71) is overexpressed inseveral malignant tumors, but no studies are available on thyroid carcinomas. Ourprevious comparative analyses of the relative distribution of transferrin inbenign versus papillary thyroid carcinoma (PTC) tissues highlighted a markedmalignancy-associated abundance of the molecule. The aim of the present study wasto evaluate whether TfR1/CD71 is also differentially expressed in benign versusmalignant thyroid tissues.METHODS: Tissue samples, including benign lesions and follicular-derivedcarcinomas, from 241 patients and a total of 35 benign and malignant freshspecimens were assayed for TfR1/CD71 expression by reversetranscriptase-polymerase chain reaction, Western blot, and immunohistochemistry.RESULTS: We found that transcription of TfR1/CD71 gene is constitutive in thyroidepithelia, but the mRNA is differently translated in benign and malignanttissues. Western blot revealed higher levels of TfR1/CD71 protein in malignantversus benign tissues. Immunohistochemically, most carcinomas exhibitedoverexpression of the receptor, predominantly in the cytoplasm of neoplasticcells. The highest expression level was detected in primary and metastaticpapillary carcinomas and anaplastic carcinomas, with positive results rangingfrom 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 beused as a marker helpful in distinguishing PTC from papillary hyperplasia andfollicular variant PTC from benign follicular-patterned lesions. Additionally,the present observations support the rationale for the use of radiolabeledtransferrin/transferrin analogs and/or anti-TfR1/CD71 antibodies for diagnosticand/or radiotherapeutic purposes in TfR1/CD71-expressing thyroid tumors.