Ulvang Marit L, Kvile Oda Fløtre, Berg Hege F, Woie Kathrine, Haldorsen Ingfrid S, Santin Alessandro D, Bertelsen Bjørn I, Krakstad Camilla, Halle Mari Kyllesø
Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
Transl Oncol. 2025 Sep;59:102453. doi: 10.1016/j.tranon.2025.102453. Epub 2025 Jun 26.
Early detection of cervical cancer (CC) generally leads to favorable prognosis; however, survival rates drop significantly for late-stage or recurrent disease with limited treatment options. Antibody-drug conjugates (ADCs) show promise across multiple cancers but remain sparsely explored in CC.
This study evaluates ADC target expression in primary and metastatic CC to identify potential ADC responders.
Membrane expression of tissue factor, TROP2 and NECTIN4 was investigated by immunohistochemistry in 522 primary and 194 metastatic CC lesions. Expression levels were scored according to the ASCO/CAP criteria and correlated with clinicopathological features and follow-up data.
Tissue factor, TROP2, and NECTIN4 membranous expression were cancer-cell specific and strong (3+) in 29 %, 37 %, and 4 %, and high (≥2+) in 48 %, 68 %, and 12 % of tumors, respectively. High TF and TROP2 expression were predominantly observed in squamous cell and adenosquamous histologies (p<0.001). Overall, 80 % of primary tumors exhibited high expression of at least one of the ADC targets. High levels of tissue factor and TROP2 were detected in 45 % and 70 % of the metastatic lesions, respectively. The proportion of lesions with high NECTIN4 expression was 12 % in primary tumors and 38 % in recurrent lesions.
The ADC targets tissue factor and TROP2 are highly expressed in primary and metastatic CC. The prevalence of high NECTIN4 expression is modest in primary tumors but increases significantly in recurrent disease. These findings support the initiation of clinical trials to evaluate safety and efficacy profiles of ADCs targeting tissue factor, TROP2 and NECTIN4 in CC.
宫颈癌（CC）的早期检测通常会带来良好的预后；然而，对于晚期或复发性疾病，由于治疗选择有限，生存率会显著下降。抗体药物偶联物（ADC）在多种癌症中显示出前景，但在CC中的研究仍较少。
本研究评估ADC靶点在原发性和转移性CC中的表达，以确定潜在的ADC反应者。
通过免疫组织化学研究了522例原发性和194例转移性CC病变中组织因子、TROP2和NECTIN4的膜表达。根据美国临床肿瘤学会/美国病理学家学会（ASCO/CAP）标准对表达水平进行评分，并与临床病理特征和随访数据相关联。
组织因子、TROP2和NECTIN4的膜表达具有癌细胞特异性，分别在29%、37%和4%的肿瘤中为强阳性（3+），在48%、68%和12%的肿瘤中为高表达（≥2+）。高TF和TROP2表达主要见于鳞状细胞和腺鳞癌组织学类型（p<0.001）。总体而言，80%的原发性肿瘤至少表达一种ADC靶点。在45%和70%的转移性病变中分别检测到高水平的组织因子和TROP2。NECTIN4高表达的病变比例在原发性肿瘤中为12%，在复发性病变中为38%。
ADC靶点组织因子和TROP2在原发性和转移性CC中高表达。NECTIN4高表达在原发性肿瘤中发生率较低，但在复发性疾病中显著增加。这些发现支持开展临床试验，以评估针对CC中组织因子、TROP2和NECTIN4的ADC的安全性和疗效。
