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  • Author: Ricardo Pujol-Borrell x
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Ian Todd, Ricardo Pujol-Borrell, Antonino Belfiore and Gian Franco Bottazzo

Abstract. The occurrence of HLA Class II expression by thyroid (and other endocrine) epithelia in autoimmune diseases suggests that these cells may facilitate their own destruction by immunogenically presenting autoantigens. This is supported by the findings that Class II+ thyrocytes can specifically stimulate virus-specific and autoreactive T cell clones, and that Class II expression by thyrocytes correlates with the occurrence of thyroid autoantibodies. A variety of factors may contribute to the regulation of Class II expression by thyrocytes: this is induced by interferon (IFN-gamma), and is enhanced by thyroid stimulating hormone (TSH) and by tumour necrosis factor (TNF). Conversely, epidermal growth factor (EGF) suppresses the induction of Class II in thyrocytes. This complex regulation is reflected in differences in HLA-D subregion expression between patients (DR > DP > DQ).

The immune-based mechanisms of thyrocyte Class II regulation are clearly applicable to the on-going disease in an infiltrated thyroid, but the possibility of nonimmune Class II induction deserves attention, particularly in identifying factors which might contribute to the initial autoimmune attack. The possible involvement of such mechanisms in autoimmunity is supported by findings in Type I diabetes in which Class II+ islet beta cells can be found in the absence of infiltration. Further evidence is provided by the observation that a proportion of thyrocytes transformed with SV40 DNA constitutively express Class II molecules.

Finally, the 'activated' state of capillary endothelial cells in organs subject to autoimmune attack suggests that they may play an important role in facilitating the autoreactive infiltration of the tissues.

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Carmela Iglesias Felip, Carles Zafon Llopis, Jordi Temprana-Salvador, Amparo García-Burillo, Xavier Serres Créixams, Enric Caubet Busquet, Isabel Roca Bielsa, Jordi Mesa Manteca, Joan Castell Conesa, José Manuel Fort López-Barajas, Ricardo Pujol-Borrell, Santiago Ramon y Cajal Agüeras and Oscar González López

Objective

Lymphadenectomy in papillary thyroid carcinoma (PTC) is controversial. It is indicated whenever metastases have been proven before or during surgery and as a prophylactic treatment in high-risk patients. However, 30–50% of cN0 patients become pN1 postoperatively. In PTC, selective-sentinel-lymph-node-biopsy (SLNB) with conventional intraoperative analysis is 8% false negative. One-step nucleic acid amplification (OSNA) is a molecular technique which allows real-time detection of mRNA encoding for cytokeratin 19. OSNA has been introduced in intraoperative analysis of several tumors to reduce false-negative rates and distinguish micrometastasis from macrometastasis. Our objective was to evaluate the impact of the introduction of OSNA in the intraoperative evaluation of the sentinel node (SN) in PTC.

Design

We analyzed a series of 35 patients subjected to SLNB.

Methods

All the dissected nodes, SN and non-SN, were evaluated with OSNA and cytology.

Results

We obtained a total of 110 SN. SLNB proved positive in 14 patients (40%) with cytology and in 23 (65.7%) with OSNA (P < 0.001). In the 29 patients with subsequent lymphadenectomy we obtained 360 lymph nodes ((52 positive in cytology (14.4%) and 107 in OSNA (29.7%)). Lymphadenectomy proved positive in 16 patients according to cytology (55%) and in 24 according to OSNA (83%) (P = 0002). The majority of patients with micrometastasis in SN showed only micrometastasis in lymphadenectomy.

Conclusions

The present study shows selective-sentinel-lymph-node-biopsy with one-step nucleic acid amplification technique to be feasible in papillary thyroid carcinoma. The quantitative nature of one-step nucleic acid amplification paves the way toward a more personalized surgical approach, limiting lymphadenectomy to patients with intraoperative evidence of macrometastasis in the sentinel node.