The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer.

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High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified.

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

Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

Objective: Pregnancy represents a favorable condition for the development of thyroid nodules, likely due to the secretion of hormones with stimulatory activity. In particular, differentiated thyroid cancer (DTC) represents the second most frequent tumor among those diagnosed during pregnancy. However, few and discordant data are available about the impact of pregnancy on tumor outcome. Methods: A total of 123 women with DTC were divided into three groups according to the timing of tumor diagnosis (group 1, at least 1 year after the delivery; group 2, during pregnancy or in the first year after delivery; and group 3, before pregnancy or nulliparity) and evaluated according to the international guidelines. Furthermore, immunohistochemical studies of estrogen receptor a (ERa) were performed in 38 papillary thyroid cancer tissues from the three groups. Results: Thyroid cancer diagnosed during pregnancy was associated with a poorer prognosis compared to tumors developed in nongravidic periods (P!0.0001). Accordingly, at the stepwise logistic regression analysis, the diagnosis of DTC during pregnancy or in the first year post partum was the most significant indicator of persistent disease (PZ0.001). Interestingly, ERa expression significantly differed among tumors of the three groups, being detected in 31% of group 1, in 87.5% of group 2, and in 0% of group 3 (PZ0.01). Conclusions: Present data indicate that pregnancy has a negative impact on the outcome of thyroid cancer. The presence of ERa in the majority of tumors diagnosed during pregnancy indicates that the poorer outcome of these cases could be related to the estrogen-mediated growth stimulus.

Background: Thyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors. Methods: We studied the expression of estrogen receptor a (ERa or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features. Results: ERa and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER-and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the 'receptor conversion' phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERa-positive primary tumors analyzed had ERa-negative metastatic lymph nodes. At the genetic analyses, BRAF V600E mutation was detected in 23.2% of the tumors

Fetal cell microchimerism (FCM) is defined as the persistence, for decades after pregnancy, of fetal cells in maternal organs and circulation without any apparent rejection. We recently reported evidence, in papillary thyroid cancer (PTC) tissues, supporting a possible role of FCM in tumor damage and repair. To extend those data at the peripheral level, 106 women with a previous male pregnancy, comprising 57 with PTC and 49 healthy controls were enrolled. The presence of circulating male DNA was assessed by the amplification of the Y chromosome-specific gene SRY, with a sensitivity of 1 male cell per 1 million female cells. Moreover, to compare the microchimeric status in blood and in tumors, the neoplastic tissues of 19 women were studied. At the blood level, a significantly lower frequency of FCM was found in parous women with PTC with respect to controls (49.1% vs. 77.6%; p 5 0.002). By PCR, male DNA was identified in the tumor tissues of 6 patients, and FISH analyses confirmed the presence of microchimeric cells (range 2.1-6.9 cells/section). In some patients, FCM was negative in the blood, whereas microchimeric cells were identified in the tumor. In conclusion, the prevalence of FCM in peripheral blood was found to be significantly lower in patients than in healthy controls. The presence of microchimeric cells in the tumors, but not at the peripheral level, supports the hypothesis that fetal cells could reside in maternal niches and could be recruited to diseased areas, where they could differentiate to regenerate damaged tissues.During pregnancy a bi-directional exchange of cells has been observed between the fetus and the mother, starting from the 4th to 6th week of gestation, and fetal cells have been documented to persist in the maternal circulation or tissues for decades. 1,2 This cells trafficking primarily includes subsets of immune cells, including pregnancy-associated progenitor cells with the capacity for multilineage differentiation. 3 Fetal cell microchimerism (FCM) is a common event in pregnancy, being detected in the peripheral blood in 20-75% of parous women 1,4-6 and in the tissues injured by neoplastic or benign diseases in 40-100% of patients. 7-12 Different hypotheses about the role of FCM in malignancies have been proposed, 13-15 whereas scarce data on microchimerism in tissue without disease are available.The role of FCM has been first studied in autoimmune diseases, such as systemic sclerosis, primary biliary cirrhosis, Sjögren syndrome, erythematous systemic lupus, Type 1 diabetes mellitus and thyroiditis. 4,10,[16][17][18][19] More recently, studies on FCM have been extended to nonautoimmune diseases, including hepatitis C, benign and malignant thyroid diseases, cervical, breast, lung, colon, uterine, ovarian, cervical cancers, and hematological malignancies. [5][6][7][8][9][11][12][13]15 Discordant data are available about the causative relevance of FCM in both autoimmune and neoplastic diseases. Briefly, in most studies FMC has been postulated to be pathogenic in autoimmune disease...