Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB201

Poster Communications

Role of inflammation in papillary thyroid carcinoma (PTC) development and progression

O. N. Sulaieva1, O. Chernenko2

1. Department of Histopathology, Laboratory of pathology "CSD Health Care", Kyiv, Ukraine. 2. Department of Pathology, Ukrainian Research and Practical Center for Endocrine Surgery, Kyiv, Ukraine.


It is accepted that frequency of PTC in higher among patients with autoimmune thyroiditis. However, it is steel unclear what mechanisms determine this relationship. The aim of the study was to assess possible immune-mediated mechanisms of PTC development and progression. 87 patients with histologically confirmed PTC were enrolled in the study, 32 of them had concurred Hashimoto's (HT) or focal thyroiditis (FT). Immunohistochemistry to the following markers was performed: CD68, CD163, MCT, CD138 and CD8 was performed. In addition, expression of VEGF and STAT6 was estimated. PTC with concurred HT or FT was associated with high number of macrophages, mast cells (MC), CD8 and plasma cells (P<0,0001). The tight association between high M2-macrophages number and lymph node metastasis was found (OR=8.56; 95%CI 2.46-28.22; P=0.0004). However, number of tumor associated CD8+ cells was not related with metastasis risk (P=0.821) that could be explained by potential PD-L1 expression. In addition, PTC with concurred HT or FT was accompanied with accumulation of numerous plasma cells, that were distributed inside the tumor foci and in lymphoid follicles around. Number of M2 macrophages tightly correlated with count of CD138+ cells, reflecting an association of M2 macrophages polarization with humoral immunity activation. M2-macrophages and MC count was related with high microvascular density (P=0.006) and VEGF expression (P<0.0001), intrathyroid invasion (P=0.03) and lymph node dissemination (P=0.005). Expression of VEGF was found in tumor cells and in stroma. VEGF expression in tumor cells varied from low to high and correlated with degree of infiltration (r=0.677; P<0.001) and number of M2 macrophages (r=0.812; P<0.0001). Thus, PTC progression is associated with humoral immunity acceleration, M2-macrophages polarization, accumulation of MC and high VEGF expression. As far as humoral immunity is mediated by IL-4, we supposed that PCT progression could be associated with changes in STAT6 expression. Normal thyroid tissue demonstrated lack of STAT6 expression. In PTC we found that in addition to numerous STAT6 positive stromal cells, there was middle to high cytoplasmic expression of STAT6 in tumor cells. Its intensity correlated with inflammatory infiltration (r=0.793; P<0.001) and was significantly higher in patients with concurred HT or FT (P=0.02). In addition, we found expression of STAT6 around tumor foci associated with infiltration and features of active thyroid tissue remodeling and cellular atypia. The similar pattern was found in patients with PTC and concurred HT - in zones of intensive infiltration and around lymphoid follicles. In conclusion, chronic inflammation accompanied with humoral immunity activation was associated with PTC progression and metastasis. One of the possible links between immune reaction and PTC could be IL-4 mediated activation of STAT6, associated with tissue remodeling and M2-macrophages polarization.

Where applicable, experiments conform with Society ethical requirements