Lin Lawrence Hsu, Hasselblatt Kathleen T, Parra-Herran Carlos, Horowitz Neil S, Berkowitz Ross S, Quade Bradley J, Elias Kevin M
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School.
Int J Gynecol Pathol. 2025 Jul 10. doi: 10.1097/PGP.0000000000001119.
Antibody-drug conjugates (ADC) are emerging therapies with promising results in the treatment of solid tumors. In this study, we aimed to evaluate biomarker expression of ADCs, including folate receptor alpha (FOLR1), Nectin-4, trophoblast cell surface antigen 2 (Trop-2), and tissue factor (TF) in a diverse cohort of gestational trophoblastic disease. Immunohistochemistry for FOLR1, Nectin-4, Trop-2, and TF was evaluated in tissue microarray of 18 complete hydatidiform moles (CHM) and whole tissue sections of 62 gestational trophoblastic neoplasia (GTN) by 2 gynecologic pathologists. Western blotting for FOLR1, Nectin-4, and Trop-2 was performed in JEG-3 and JAR choriocarcinoma cell lines, 2 CHM and 3 GTN clinical samples. Results: The overall immunohistochemical positive rate in GTN was 11% for FOLR1, 59% for Nectin-4, 38% for Trop-2, and 26% for TF. Choriocarcinomas showed 27% positivity for FOLR1, 75% for Nectin-4, 40% for Trop-2, and 25% for TF. Epithelioid trophoblastic tumors (ETT) were positive for Nectin-4 in 58%, for Trop-2 in 79%, and for TF in 67% of cases. Placental site trophoblastic tumors were positive only for Nectin-4 (23% of cases). In CHM, only Nectin-4 revealed a higher degree of expression and limited staining for the other markers. Western blotting showed FOLR1 expression in CHM, JEG-3, and JAR; Nectin-4 in CHM and PSTT; and Trop-2 in CHM, JEG-3, and choriocarcinoma. Conclusion: A subset of GTN shows expression for FOLR1, Nectin-4, Trop-2, and TF, particularly choriocarcinoma and ETT. These results suggest that patients with GTN could potentially benefit from ADC treatment.
抗体药物偶联物（ADC）是正在兴起的治疗方法，在实体瘤治疗中取得了令人鼓舞的成果。在本研究中，我们旨在评估ADC的生物标志物表达情况，包括在不同类型的妊娠滋养细胞疾病队列中评估叶酸受体α（FOLR1）、Nectin-4、滋养层细胞表面抗原2（Trop-2）和组织因子（TF）的表达。两名妇科病理学家在18例完全性葡萄胎（CHM）的组织芯片以及62例妊娠滋养细胞肿瘤（GTN）的全组织切片中对FOLR1、Nectin-4、Trop-2和TF进行了免疫组织化学评估。在JEG-3和JAR绒毛膜癌细胞系、2例CHM和3例GTN临床样本中进行了FOLR1、Nectin-4和Trop-2的蛋白质印迹分析。结果：GTN中FOLR1的免疫组织化学总体阳性率为11%，Nectin-4为59%，Trop-2为38%，TF为26%。绒毛膜癌中FOLR1阳性率为27%，Nectin-4为75%，Trop-2为40%，TF为25%。上皮样滋养细胞肿瘤（ETT）中Nectin-4阳性率为58%，Trop-2为79%，TF为67%。胎盘部位滋养细胞肿瘤仅Nectin-4阳性（23%的病例）。在CHM中，只有Nectin-4显示出较高程度的表达，其他标志物染色有限。蛋白质印迹分析显示CHM、JEG-3和JAR中有FOLR1表达；CHM和胎盘部位滋养细胞肿瘤中有Nectin-4表达；CHM、JEG-3和绒毛膜癌中有Trop-2表达。结论：一部分GTN显示出FOLR1、Nectin-4、Trop-2和TF的表达，尤其是绒毛膜癌和ETT。这些结果表明GTN患者可能从ADC治疗中获益。
