Thyroglobulin as a negative marker for malignancy in canine and human breast tumors

Abstract

Canine mammary gland tumors (CMTs) are the most common tumor type in female dogs. This study evaluated the expression pattern and role of thyroglobulin (Tg) in CMT and in human breast cancer (HBC). CMT samples were subjected to fine‐needle aspiration, primary cell culture, and histopathology. The expression level of Tg was higher in benign CMT than in malignant CMT (mCMT) primary cells, particularly in the epithelial lineage. Moreover, treatment with Tg enhanced the sensitivity of doxorubicin in mCMT epithelial cells and mitigated proinflammatory response by increasing nuclear factor erythroid 2‐related factor 2 (Nrf2). The proximal region of the Tg promoter was hypermethylated in mCMT epithelial cells, silencing Tg expression with concurrent downregulation of Nrf2‐mediated antioxidant signaling. An identical pattern of Tg expression was observed in cytological and tissue samples. Tissue microarray analysis showed that Tg was highly expressed in normal and benign tissues when compared with their malignant counterparts, which was diminished along with higher histological grades. The survival rate was significantly higher in HBC patients with high Tg expression than those with low Tg expression. This study also showed that the progression of HBC is accompanied by the reduction of Tg expression along with augmentation of proinflammatory signaling. Our data suggested that Tg could be a negative indicator of malignancy in canine and human breast neoplasia

Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis

“…Thyroid cancer is a common endocrine malignancy, and the incidence of thyroid cancer has increased significantly in recent decades (1). In 2020, the incidence of thyroid cancer ranks 9th in the global cancer incidence spectrum, with the global incidence of thyroid cancer being 10.1/100,000 women, 3.1/100,000 men, and 586,200 new cases (2). From 2005 to 2016, the incidence and mortality of thyroid cancer in China showed an increasing trend over time (3).…”