Imunoexpressão de proteínas relacionadas à via hippo em carcinomas papilíferos de tireoide

Abstract

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland. Although these lesions generally have an excellent prognosis, there are cases that present aggressive clinicopathological characteristics, with a high rate of lymph node metastasis and recurrence. Given this, new molecular biomarkers have been researched with the aim of better clarifying the biological and molecular processes involved in the development and progression of this neoplasm. Among them, the YAP, LATS2, and TEAD proteins, components of the Hippo Pathway (HP), stand out, which is essential in various biological processes and also participates in the carcinogenesis process when the pathway is deregulated. Therefore, this research aimed to evaluate the related proteins YAP, LATS2, and TEAD in PTCs, to verify whether these molecules can influence the biological behavior of these lesions. The sample consisted of 31 cases of PTCs and 5 follicular adenomas (control group). Clinicopathological information was collected and correlated with the immunoexpression of the YAP, LATS2, and TEAD proteins in these lesions. The evaluation of the staining was performed in the nucleus and cytoplasm, where cases with more than 20% of the nuclei stained for each of the molecules were considered positive. Regarding the cytoplasm, the intensity for YAP1 and LATS2 was evaluated. In this compartment, cases were classified as negative (no staining), weak (light brown staining), and strong (dark brown staining). Data were subjected to statistical analysis using Pearson's Chi-square and Fisher's Exact tests, with a significance level set at 5% (p < 0.05). The immunoexpression analysis showed that all PTC cases (100%) exhibited nuclear positivity for YAP. A significant association was also found between strong cytoplasmic YAP expression and PTC cases compared to the control group (p = 0.001). For LATS2, low cytoplasmic expression was observed in most PTC cases (58.1%). TEAD showed higher nuclear positivity (p = 0.029) in PTC cases. No statistically significant associations with clinicopathological data were found. The lower cytoplasmic expression of LATS2 in PTCs suggests that this protein may not regulate YAP, leading to its nuclear translocation. The elevated nuclear expression of YAP and TEAD indicates possible nuclear interaction. Therefore, the cytoplasmic subregulation of LATS2 and the nuclear YAP-TEAD interaction may influence PTC tumorigenesis.