Altered expression of autophagy-related molecules and β-catenin in different subtypes of thyroid cancer: co-localization in intranuclear cytoplasmic inclusions.

Abstract

This study aimed to clarify the expression levels of autophagy-related molecules, such as β-catenin, LC3B, and p62, in thyroid carcinoma (TC) cases of different histological types and clinicopathological characteristics. A total of 70 surgically resected thyroid nodules, including 43 papillary thyroid carcinoma (PTC), and other control groups such as five follicular adenoma (FA), five hyalinizing trabecular tumor (HTT), five follicular TC (FTC), six poorly differentiated TC (PDTC), and six anaplastic follicular cell-derived thyroid carcinoma (ATC), were analyzed by dual-color immunofluorescence for β-catenin, LC3B, and p62. Statistical analyses were used to determine the association of autophagy-related molecules with BRAF^V600E/TERT promoter mutations, Ki-67 labeling index, and clinicopathological characteristics. p62 immunoreactivity was most frequently observed in PTC, particularly in classical and tall cell subtypes. This protein appeared to co-localize with LC3B and β-catenin in intranuclear cytoplasmic inclusions (INIs) of PTC. Conversely, p62 expression was rarely observed in either FTC or PDTC. The expression levels of p62 and its co-localization with β-catenin and LC3B correlated significantly with the presence of the BRAF^V600E mutation. Frequent co-localization of dot-shaped perinuclear β-catenin signals with a component of the trans-Golgi apparatus in tall cell PTC subtype was also observed. This study revealed differences in the expression patterns of β-catenin, LC3B, and p62 among different TC types. Abnormal β-catenin expression may be linked to autophagy dysfunction, which triggers genomic instability and promotes tumor aggressiveness. These autophagy-related molecules may be cooperatively associated with INI formation during PTC carcinogenesis.