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Fetal Cell Microchimerism in Papillary Thyroid Cancer: A Possible Role in Tumor Damage and Tissue Repair

¹ Department of Medical Sciences and Endocrine Unit, University of Milan and Fondazione Policlinico Istituto Di Ricovero e Cura a Carattere Scientifico, ² Department of Biology and Genetics for Medical Sciences, University of Milan and Laboratory of Medical Cytogenetics and Molecolar Genetics, Istituto Auxologico Italiano Istituto Di Ricovero e Cura a Carattere Scientifico, ³ Pathology Unit, Department of Medicine, Surgery and Dentistry, University of Milan, Ospedale S. Paolo and Fondazione Policlinico Istituto Di Ricovero e Cura a Carattere Scientifico, and ⁴ Endocrine Surgery Unit, Fondazione Policlinico Istituto Di Ricovero e Cura a Carattere Scientifico, Milan Italy

Requests for reprints: Laura Fugazzola, Endocrine Unit, Pad. Granelli, Fondazione Policlinico Istituto Di Ricovero e Cura a Carattere Scientifico, Via F. Sforza, 35, 20122 Milan, Italy. Phone: 39-02-55033498; Fax: 39-02-50320605; E-mail: l.fugazzola{at}policlinico.mi.it.

Key Words: immuno-FISH • microchimerism • papillary thyroid cancer

Fetal cells enter the maternal circulation during pregnancy and can persist in the maternal blood or tissues for decades, creating a physiologic microchimerism. Because papillary thyroid cancer (PTC) is more frequent in women, the role of persisting fetal male cells in this tumor has been investigated. Tumor tissue specimens were obtained from 63 women with PTC who had a male pregnancy before the diagnosis. Male cells, identified by PCR amplification of a male-specific gene, the sex-determining region Y, was detected in 47.5% of women. By fluorescence in situ hybridization (FISH) analyses, the total number of microchimeric cells was significantly higher in neoplastic tissue than in controlateral normal sections. By combined FISH and immunohistochemistry (immuno-FISH), male cells expressing thyroglobulin were found in tumor and normal tissues, whereas male microchimeric cells stained with the CD45 antigen were detected only in tumor sections. Microchimeric cells negative for either marker were detected both in tumor and normal tissues. Moreover, both CD45⁺ and Tg⁺ fetal cells did not express MHC II antigens. In conclusion, fetal microchimerism has been documented in a high proportion of women with PTC. The immuno-FISH studies indicate that CD45⁺/MHC II^– male cells found in neoplastic tissues might be committed to destroy tumor cells, whereas Tg⁺/MHC II^– cells could have a repair function. Finally, microchimeric cells negative for either CD45 or Tg could have "progenitor-like" properties able to transdifferentiate in different cellular types. Although a pathogenetic mechanism cannot be excluded, the whole of the present results indicates a protective role of microchimerism in thyroid cancer. [Cancer Res 2008;68(20):8482–8]