An association between Hashimoto thyroiditis (HT) and thyroid carcinoma has been postulated for decades, although definitive molecular links remain elusive. Activation of the RET/PTC oncogene (typical of papillary thyroid carcinoma) has been reported in both non-neoplastic and neoplastic HT thyroid follicular cells (Tallini et al. 2006), but the issue is still controversial. To contribute new insight to this issue, we have investigated RET rearrangement on 207 fine needle aspiration biopsies on unselected nodules from 168 patients to 38 corresponding surgical samples. IFISH with a homebrew break-apart DNA probe was used. Normal tissue nuclei cutoff value (mean ± 3DS) was 3%. In addition, RET/PTC was investigated by RT-PCR. Coexistent overt autoimmune thyroid disease (AITD) was assessed by serological (antithyroid autoantibodies, ATA), clinical and echographic data. RET breakage (FISH+) was observed in 6.3% samples. RET/PTC was confirmed by RT-PCR (RTPCR+) in 23% FISH+ nodules. RT-PCR+ corresponded to FISH+ value ≥6.8%. No correlation between RET rearrangement and ATA (5/92 nodules ATA+, 8/115 ATA−) or between AITD (6/78 AITD+, 7/129 AITD−) was observed. Nodules with FISH+ were observed along the whole cytological spectrum, with prevalence significantly higher in suspect or malignant cytology (13.6% TIR 3–5 vs. 3.1% TIR 2 nodules). Seven of 13 FISH+ nodules were surgically removed and available for I-FISH. FISH+ was confirmed in three samples, classified as PTC classic type. Our results suggest no association between RET rearrangement and HT. The percentage of FISH+ nodules increases according to the risk of malignancy. The difference between I-FISH and RT-PCR results was observed, presumably due to the sensitivity of I-FISH strategy. Since we detected RETPTC m-RNA transcript in ≥6.8% FISH+ samples, the oncogenic potential of nodules below this value remains to be clarified, and FISH+ nodules with benign cytology should be considered for a careful follow-up. Supported by PRIN 2007 and Fondazione Banco di Sardegna.
RET/PTC rearrangements in hashimoto’s thyroiditis nodules: contribution to an ongoing debate.
CARIA, PAOLA;FRAU, DANIELA VIRGINIA;DETTORI, TINUCCIA;BOI, FRANCESCO;MARIOTTI, STEFANO;VANNI, ROBERTA
2011-01-01
Abstract
An association between Hashimoto thyroiditis (HT) and thyroid carcinoma has been postulated for decades, although definitive molecular links remain elusive. Activation of the RET/PTC oncogene (typical of papillary thyroid carcinoma) has been reported in both non-neoplastic and neoplastic HT thyroid follicular cells (Tallini et al. 2006), but the issue is still controversial. To contribute new insight to this issue, we have investigated RET rearrangement on 207 fine needle aspiration biopsies on unselected nodules from 168 patients to 38 corresponding surgical samples. IFISH with a homebrew break-apart DNA probe was used. Normal tissue nuclei cutoff value (mean ± 3DS) was 3%. In addition, RET/PTC was investigated by RT-PCR. Coexistent overt autoimmune thyroid disease (AITD) was assessed by serological (antithyroid autoantibodies, ATA), clinical and echographic data. RET breakage (FISH+) was observed in 6.3% samples. RET/PTC was confirmed by RT-PCR (RTPCR+) in 23% FISH+ nodules. RT-PCR+ corresponded to FISH+ value ≥6.8%. No correlation between RET rearrangement and ATA (5/92 nodules ATA+, 8/115 ATA−) or between AITD (6/78 AITD+, 7/129 AITD−) was observed. Nodules with FISH+ were observed along the whole cytological spectrum, with prevalence significantly higher in suspect or malignant cytology (13.6% TIR 3–5 vs. 3.1% TIR 2 nodules). Seven of 13 FISH+ nodules were surgically removed and available for I-FISH. FISH+ was confirmed in three samples, classified as PTC classic type. Our results suggest no association between RET rearrangement and HT. The percentage of FISH+ nodules increases according to the risk of malignancy. The difference between I-FISH and RT-PCR results was observed, presumably due to the sensitivity of I-FISH strategy. Since we detected RETPTC m-RNA transcript in ≥6.8% FISH+ samples, the oncogenic potential of nodules below this value remains to be clarified, and FISH+ nodules with benign cytology should be considered for a careful follow-up. Supported by PRIN 2007 and Fondazione Banco di Sardegna.
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