Endocrine Abstracts

Introduction: Long pentraxin 3 (PTX3), a protein cells produce in response to several inflammatory stimuli, is essential in innate immunity, controlling inflammation, tissue remodeling, and cancer dynamics. PTX3 promotes the migration and invasion of cells in different tumor models. This study aims to (I) immunohistochemically assess the presence and distribution of PTX3 in tissue samples from non-medullary thyroid cancer (NMTC) and (II) (TC) to determine the differences of circulating PTX3 in patients with NMTC vs patients with benign goiters.

Methods: We prospectively included 55 patients (41 preoperatively, 14 with recurrent active disease) with various subtypes of NMTC: 42 with papillary, 3 with follicular, 4 with oncocytic, 4 with anaplastic (ATC), 2 with poorly differentiated (PDTC). The control group consisted of 32 patients with multinodular goiter. Patients with chronic systemic inflammatory diseases (such as rheumatologic diseases), other active neoplasms, active infections, or pregnancy were excluded. PTX3 plasma levels were analyzed using ELISA. Local PTX3 and CD68 expression were assessed by co-staining on paraffin-embedded tissue in a patient with ATC with a positive somatic v600E BRAF mutation and a patient with goiter.

Results: No significant differences in PTX3 plasma levels between the control group and non-medullary differentiated TC were found. PTX3 plasma level in patients with ATC was significantly higher compared to control, and compared to the rest of the TC subtypes, including the aggressive histological subtypes. The plasma level of PTX3 did not correlate with tumor load (defined as the sum of all tumoral foci). There were no significant differences between patients with recurrence and those included preoperatively. The intensity and quantitative expression of PTX3 were higher in ATC, both interstitial and cellular expression, compared to normal thyroid tissue or goiter where immunostaining for PTX3 was virtually absent, with sparse and faint staining. The IHC expression of CD68 was also diffusely increased in ATC compared to goiter, suggesting infiltration by tumor-associated macrophages (TAMs). Less than 10% of the cells were double-positive for PTX3 and CD68 suggesting another source of PTX3 than TAMs.

Discussions and Conclusions: Our findings highlight significantly elevated PTX3 levels in ATC, both in plasma and in tumor tissue, compared to other TC types and control subjects. The low number of double-positive TAMs suggests that PTX3 might likely be produced by tumoral cells, stromal cells, or other immune cells. Further investigation is needed to consolidate the significance of PTX3 in ATC and its effect on the tumor microenvironment.