Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions
Background: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325001846 |
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| author | Marit L. Ulvang Oda Fløtre Kvile Hege F. Berg Kathrine Woie Ingfrid S. Haldorsen Alessandro D. Santin Bjørn I. Bertelsen Camilla Krakstad Mari Kyllesø Halle |
| author_facet | Marit L. Ulvang Oda Fløtre Kvile Hege F. Berg Kathrine Woie Ingfrid S. Haldorsen Alessandro D. Santin Bjørn I. Bertelsen Camilla Krakstad Mari Kyllesø Halle |
| author_sort | Marit L. Ulvang |
| collection | DOAJ |
| description | Background: 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. Objective: This study evaluates ADC target expression in primary and metastatic CC to identify potential ADC responders. Study Design: 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. Results: 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. Conclusions: 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. |
| format | Article |
| id | doaj-art-89ed5724beca4b39b360d680f9f639b4 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-89ed5724beca4b39b360d680f9f639b42025-08-20T03:32:46ZengElsevierTranslational Oncology1936-52332025-09-015910245310.1016/j.tranon.2025.102453Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesionsMarit L. Ulvang0Oda Fløtre Kvile1Hege F. Berg2Kathrine Woie3Ingfrid S. Haldorsen4Alessandro D. Santin5Bjørn I. Bertelsen6Camilla Krakstad7Mari Kyllesø Halle8Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, NorwayCentre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, NorwayCentre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, NorwayDepartment of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, NorwayMohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway; Section of Radiology, Department of Clinical Medicine, University of Bergen, Bergen, NorwayDepartment of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Pathology, Haukeland University Hospital, Bergen, NorwayCentre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, NorwayCentre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Corresponding author.Background: 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. Objective: This study evaluates ADC target expression in primary and metastatic CC to identify potential ADC responders. Study Design: 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. Results: 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. Conclusions: 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.http://www.sciencedirect.com/science/article/pii/S1936523325001846Cervical cancerADC targetTissue factorNECTIN4TROP2Metastatic lesions |
| spellingShingle | Marit L. Ulvang Oda Fløtre Kvile Hege F. Berg Kathrine Woie Ingfrid S. Haldorsen Alessandro D. Santin Bjørn I. Bertelsen Camilla Krakstad Mari Kyllesø Halle Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions Translational Oncology Cervical cancer ADC target Tissue factor NECTIN4 TROP2 Metastatic lesions |
| title | Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions |
| title_full | Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions |
| title_fullStr | Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions |
| title_full_unstemmed | Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions |
| title_short | Co-expression of tissue factor, TROP2, and NECTIN4 in primary and matched metastatic cervical cancer lesions |
| title_sort | co expression of tissue factor trop2 and nectin4 in primary and matched metastatic cervical cancer lesions |
| topic | Cervical cancer ADC target Tissue factor NECTIN4 TROP2 Metastatic lesions |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325001846 |
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