Thyroid autoimmunity and thyroid cancer: pathological and molecular study in a longitudinal series of unselected nodules.

Boi F;Caria P;Borghero A;Frau DV;Cappai A;Dettori T;Riola A;Maurelli I;Lai ML;Calò PG;Nicolosi A;Vanni R;Mariotti S.

2011-01-01

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Abstract

AIM: To confirm the potential association between autoimmune thyroid diseases (AITD) and papillary thyroid carcinoma (PTC) in a prospective study in unselected thyroid nodules (TN). PATIENTS AND METHODS: One-hundred-eighty-four patients (235 TN) consecutively submitted to fine-needle aspiration cytology (FNAC), fully evaluated for associated AITD. In most FNAC samples, BRAFV600E mutation was evaluated by PCR and RET-PTC rearrangements by PCR and interphase fluorescence in situ hybridization (I-FISH), using a newly developed homebrew dual-color-breakpart RET probe. In 61 operated patients (75 TN), histology and lymphocytic thyroid infiltration (LTI) description were available. RESULTS: Higher prevalence of suspicious/malignant cytology was found in AITD+ TN (22.6% vs 9.8% in AITD-, p<0.01). Prevalence of PTC in operated TN was higher in AITD+ (68.8%) than in AITD- (44.2%, p<0.05) and LTI was found in 66% of malignant vs 34% of benign TN (p <0.05). BRAFV600E mutation was found in 11/93 (11.8%) AITD+ vs 2/142 (1.4%) AITD- TN (p<0.001), all PTC. BRAFV600E mutation was found in 11/22 (50%) AITD+ and in 2/17 (11.8%; p<0.02) AITD- PTC. RET-PTC rearrangements were found by PCR only in 3 FNAC (one AITD+ and two AITD-) all showing a separate breakapart I-FISH signal in ≥ 6.8% nuclei. When compared to normal thyroid, broken signal (cutoff ≥3%, mean±3DS), was found in a larger number of FNAC distributed along the whole cytological spectrum, with higher prevalence in indeterminate to suspicious/malignant (13.6%) vs benign (3.1%) cytology, but no correlation was observed between broken I-FISH signal and AITD. CONCLUSIONS: A significant association between AITD and PTC was confirmed in a prospective study of TN submitted to FNAC. This association does not appear to be mediated by RET-PTC rearrangements. The higher prevalence of BRAFV600E mutation in PTC associated with AITD will deserve further investigation.