The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study

Abstract

To develop a new therapeutic strategy against thyroid cancer (TC), the expression of both substance P (SP) and neurokinin-1 receptor (NK-1R) must be demonstrated in TC cells. This study aims to examine by immunohistochemistry, the localization of SP and the NK-1R in human TC samples (papillary, follicular, medullary, anaplastic), in metastasis and in healthy thyroid samples. SP and the NK-1R were expressed in all normal and TC samples. In healthy glands, SP was located in follicular cells (nucleus) and colloid and NK-1R in follicular cells (cytoplasm) and stroma. In TC samples, SP was visualized in follicular cells (nucleus and cytoplasm), stroma and colloid and NK-1R in follicular cells (cytoplasm), stroma and colloid. A semiquantitative scoring system (Allred Unit Scoring System) was applied. The expression (Allred total score) of SP and NK-1R was weaker in normal thyroid glands than in TC. In comparison with TC samples, a lower intensity/proportion of SP (nucleus and cytoplasm of follicular cells; stroma) was observed in normal samples. By contrast, in the colloid of TC samples the presence of SP was lower than in normal samples. In comparison with TC samples, the presence of the NK-1R in the cytoplasm of follicular cells and colloid was lower in normal thyroid samples, whereas the expression of this receptor in the stroma was higher. The results reported in this study suggest that the NK-1R could be a new target for the treatment of TC and use of the NK-1R antagonists could serve as a new anti-TC therapeutic strategy.

Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis

“…Currently, research is focused on the prognostic and therapeutic value of emerging molecular biomarkers that may serve as a complement in clinical practice [ 7 , 8 ]. Accumulated evidence suggests that Substance P (SP)/NK-1R alterations play a key role in head and neck oncogenesis, particularly in laryngeal carcinomas and oral squamous cell carcinomas [ 9 , 10 , 11 , 12 ].…”

Acute diffuse thyroid swelling after fine‐needle aspiration: A case report and review of the literature

“…Substance P (SP), an undecapeptide belonging to the tachykinin family of peptides, is expressed throughout the entire body. 20 SP is released from nerve endings and causes biological actions, such as neurogenic inflammation, pain, mitogenesis, and regulation of the cardiovascular system. 21 A previous study showed the localization of SP by immunohistochemistry in both human thyroid cancer and in the healthy thyroid gland.…”

“…21 A previous study showed the localization of SP by immunohistochemistry in both human thyroid cancer and in the healthy thyroid gland. 20 Therefore, it is possible that such biological actions are induced by the FNA of the thyroid. On the other hand, Van den Bruel et al reported that acute thyroid swelling after FNA in a patient with medullary carcinoma caused vasodilation and blood vessel hyperpermeability due to the local release of calcitonin generelated peptide, a potent endogenous vasodilator produced by the nervous system and universally expressed by medullary thyroid cancer.…”

Immunohistochemical basigin expression level in thyroid cancer tissues

“…Recent studies have confirmed a few molecular markers that have allowed better understanding of the molecular mechanisms of TC, for instance, BRAF and RAS point mutations, RET/PTC and PAX8/PPAR gene rearrangements, etc [5][6][7]. In addition, the latest study found that Substance P/neurokinin-1 receptor (SP/NK-1R) system was over-expressed in TC than that in normal thyroid tissues via immunohistochemical study, which could promote the migration and invasion of cancer cells [8]. Targeting certain molecules associated with initiation and progression of TC will be a significant and promising research area.…”