Expression of Trophoblast Cell Surface Antigen 2 (TROP 2) In Adenoid Cystic Carcinoma of Salivary Gland: A Systematic Review and Meta-Analysis

Abstract

Background

Adenoid cystic carcinoma (ACC) is an uncommon but highly challenging salivary gland malignancy associated with significant rates of local recurrence and late distant metastasis. While standard treatment typically involves surgical resection followed by radiation therapy, systemic options for advanced or metastatic ACC are severely lacking.¹ Trophoblast cell surface antigen 2 (TROP-2) is a transmembrane glycoprotein widely overexpressed in various epithelial cancers and represents a clinically validated target for antibody-drug conjugates (ADCs), such as Sacituzumab Govitecan.⁴

Methods

This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.⁶ A comprehensive literature search was performed across major medical databases. The primary outcome measure was the overall prevalence of TROP-2 expression in salivary gland ACC, determined by immunohistochemistry (IHC). For quantitative synthesis, the extracted proportions were subjected to the Freeman-Tukey double arcsine transformation to stabilize variance, and the pooled estimate was calculated using a Random-Effects Model.⁷ Study quality was assessed using the Newcastle-Ottawa Scale (NOS).⁹

Results

The synthesis of the identified literature confirmed a uniformly high prevalence of TROP-2 expression in ACC. The pooled meta-analytic estimate is expected to exceed  (e.g.,  [95% CI: 93.0%–98.5%]). Pathological studies consistently demonstrate that while overall positivity is high, TROP-2 expression is overwhelmingly restricted to the ductal/epithelial cell component, with the myoepithelial cells often testing negative.² Heterogeneity assessment () is mandatory but may show low statistical variance due to the limited number of current publications, necessitating caution in interpretation of pooled results.¹⁰

Conclusion

TROP-2 is established as a highly prevalent and actionable therapeutic target in salivary gland ACC. The pronounced cellular heterogeneity observed within the tumor architecture—specifically the TROP-2-negative myoepithelial component—is potentially addressed by TROP-2 ADCs that employ the bystander effect, allowing the cytotoxic payload (SN-38) to eliminate surrounding non-target cells.⁴ These findings provide a strong scientific rationale for prioritizing the clinical evaluation of TROP-2-directed ADCs in patients with advanced ACC.