Assessment of delta-like ligand 3 (DLL3) immunostaining in neuroendocrine tumors of the gynecological tract and comparing expression with other high-grade gynecological malignancies.

内容摘要

Neuroendocrine tumors (NETs) of the gynecologic tract are diagnostically challenging because of their heterogeneity. Delta-like ligand 3 (DLL3), an inhibitory Notch receptor ligand, is frequently overexpressed in NETs and has emerged as a potential diagnostic and therapeutic target. This study evaluated DLL3 expression in 76 paraffin-embedded tissue samples from 74 patients, including cervical and ovarian small cell carcinomas/NETs, cervical large cell carcinoma/NET, metastatic NETs, dedifferentiated/undifferentiated carcinomas, carcinosarcomas, and high-grade serous carcinomas. DLL3 positivity was defined by cytoplasmic staining and assessed by staining intensity (0-3+) and percentage of positive tumor cells. DLL3 expression was detected in 83% of cervical small cell carcinomas/NETs, 67% of ovarian small cell carcinomas/NETs, and 100% of cervical large-cell carcinoma/NETs, all showing strong (3+) staining and seen in 5% to 100% of the tumor cells. Metastatic NETs demonstrated lower expression (14%, 3+), which was seen in 90% of the tumor cells. Among dedifferentiated/undifferentiated carcinomas, 60% showed DLL3 positivity in scattered undifferentiated foci with staining intensities ranging from 1+ to 3+. DLL3 expression was also identified in 62% of carcinosarcomas within scattered foci of sarcomatous areas, with 2+ to 3+ intensity. In contrast, high-grade serous carcinomas lacked DLL3 expression. These findings demonstrate frequent DLL3 expression in gynecologic NETs and selected dedifferentiated malignancies, supporting DLL3 as a promising diagnostic marker and potential therapeutic target in gynecologic cancers.