The Significance of TROP2 Expression in Predicting <i>BRAF</i> Mutations in Papillary Thyroid Carcinoma

Abstract

Pancreatic cancer is one of the most devastating human malignancies. Despite considerable research efforts, it remains resistant to almost all available treatment regimens. The human trophoblast cell-surface antigen, TROP2, was found to be strongly expressed in a variety of human epithelial cancers, correlating with aggressiveness and poor prognosis. TROP2 antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series (n ¼ 197) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated using Kaplan -Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. TROP2 overexpression was observed in 109 (55%) of 197 pancreatic cancer patients and was significantly associated with decreased overall survival (Po0.01). By univariate analysis, TROP2 overexpression was found to correlate with the presence of lymph node metastasis (P ¼ 0.04) and tumour grade (P ¼ 0.01). Furthermore, in the subgroup of patients treated surgically with curative intent, TROP2 overexpression significantly correlated with poor progression-free survival (Po0.01). Multivariate analyses revealed TROP2 to be an independent prognosticator. These findings suggest for the first time that TROP2 could be a novel prognostic biomarker for pancreatic cancer. Targeting TROP2 might be a useful treatment approach for patients with pancreatic cancer overexpressing this cell-surface marker.

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

“…Previous studies have linked TROP2 to increased tumor growth and demonstrated TROP2 to be a candidate tumor prognostic marker in various tumors. TROP2 is found to be overexpressed in the majority of human epithelial cancers, including pancreatic cancer, gastric cancer, lung cancer, ovarian cancer, and colorectal cancers (10,14,32). Chen et al (33) investigated the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator proteins in 93 patients with gallbladder cancer (GBC) and demonstrated that increased expression of TROP2 in GBC is associated significantly with aggressive progression and poor prognosis.…”

“…Human trophoblast cell surface antigen 2 (TROP2) is a 36-kDa single-pass transmembrane protein encoded by the tumor-associated calcium signal transducer 2 (Tacstd2) gene, with low to no expression in normal tissues (10)(11)(12)(13). Accumulating studies have demonstrated TROP2 to be a candidate tumor prognostic marker, which was highly expressed by various tumors, such as pancreatic cancer (14,15), gastric cancer (11,16), lung cancer (17,18), ovarian cancer (19), and colorectal cancers (20).…”

“…TROP2 overexpression correlates with increased tumor recurrence, invasiveness, and poor clinical outcome (21)(22)(23). Although TROP2 has mostly been reported to be highly expressed in epithelial cancers, previous studies have also found TROP2 expression in stem cells in various tissue types, such as human and mouse prostate (10,24). In addition, TROP2 is also expressed in bone tissues and regulates the proliferation and differentiation of bone marrow stromal cells (25)(26)(27).…”

Evaluation of Diagnostic Utility of Immunohistochemistry Markers of TROP-2 and HBME-1 in the Diagnosis of Thyroid Carcinoma

“…Its overexpression is seen in the majority of human carcinomas, including colorectal, gastric, and pancreatic adenocarcinoma, squamous cell carcinoma of the oral cavity, non-small cell carcinoma of the lung, and endometrial and ovarian cancers, and rarely in normal tissue. TROP-2 overexpression in carcinoma is related to poor prognosis and aggressive behavior [6, 8, 11], but no single marker is sensitive nor specific for differentiation between benign and malignant thyroid neoplasm. Therefore, in this study, we evaluated the diagnostic utility of a panel consisting of HBME-1 and TROP-2 for differentiation between benign and malignant thyroid lesions.…”

“…HBME-1 is a membrane antigen found in the mesothelial cells and in lung, breast, and pancreas adenocarcinomas. TROP-2, also known as tumor-associated calcium signal transducer 2 (TAC-STD2) [6, 8, 11], is a 35-kDa, 323 amino acid, type 1 transmembranous glycoprotein. It is identified in choriocarcinoma and trophoblastic cells.…”