Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients?
Variant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as...
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/18/4411 |
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| author | Severin Rodler Lennert Eismann Boris Schlenker Jozefina Casuscelli Isabel Brinkmann Andrea Sendelhofert Raphaela Waidelich Alexander Buchner Christian Stief Gerald Bastian Schulz Stephan Ledderose |
| author_facet | Severin Rodler Lennert Eismann Boris Schlenker Jozefina Casuscelli Isabel Brinkmann Andrea Sendelhofert Raphaela Waidelich Alexander Buchner Christian Stief Gerald Bastian Schulz Stephan Ledderose |
| author_sort | Severin Rodler |
| collection | DOAJ |
| description | Variant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as a highly interesting target in BC and might guide therapeutic application of antibody–drug conjugates (ADC). We therefore aimed to investigate expression patterns and prognostic value of Nectin-4 in variant histologies of BC. A single-center retrospective analysis was conducted of patients who underwent radical cystectomy (RC) for BC and revealed variant histologies of BC in the final specimens. Immunohistochemical staining for Nectin-4 was performed on tissue microarrays with 59 SCC, 22 ADENO, and 24 SARCO, and Nectin-4 expression was scored using the histochemical scoring system (H-score). Overall survival (OS) and progression-free survival (PFS) was calculated by Kaplan–Meier method. Median expression of Nectin-4 was 150 (range 0–250) in SCC, 140.5 (range 30–275) in ADENO, and 10 (0–185) in SARCO, with significantly lower levels for SARCO compared to SCC or ADENO (<i>p</i> < 0.001). For SCC, ADENO or SARCO no differences regarding OS or PFS were observed based on Nectin-4 expression levels (<i>p</i> > 0.05). Multivariate analysis revealed nodal stage as an independent prognostic factor for OS and PFS and metastases for PFS but not Nectin-4 expression. In conclusion, Nectin-4 was not prognostic in histological subtypes of BC in our study cohort. However, the high expression of Nectin-4 in SCC and ADENO might guide future treatment with novel Nectin-4-directed ADCs and provide this high-risk patient collective with a new promising therapeutic option. Testing Nectin-4 expression as a biomarker should be considered in trials with SARCO, where low Nectin-4 expression has been observed. |
| first_indexed | 2024-03-10T00:30:24Z |
| format | Article |
| id | doaj.art-46652bfd8b6f47a38fd03a19367ec178 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:30:24Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-46652bfd8b6f47a38fd03a19367ec1782023-11-23T15:26:49ZengMDPI AGCancers2072-66942022-09-011418441110.3390/cancers14184411Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients?Severin Rodler0Lennert Eismann1Boris Schlenker2Jozefina Casuscelli3Isabel Brinkmann4Andrea Sendelhofert5Raphaela Waidelich6Alexander Buchner7Christian Stief8Gerald Bastian Schulz9Stephan Ledderose10Department of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Pathology, Ludwig Maximilian University Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Urology, University Hospital of Munich, 81377 Munich, GermanyDepartment of Pathology, Ludwig Maximilian University Munich, 81377 Munich, GermanyVariant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as a highly interesting target in BC and might guide therapeutic application of antibody–drug conjugates (ADC). We therefore aimed to investigate expression patterns and prognostic value of Nectin-4 in variant histologies of BC. A single-center retrospective analysis was conducted of patients who underwent radical cystectomy (RC) for BC and revealed variant histologies of BC in the final specimens. Immunohistochemical staining for Nectin-4 was performed on tissue microarrays with 59 SCC, 22 ADENO, and 24 SARCO, and Nectin-4 expression was scored using the histochemical scoring system (H-score). Overall survival (OS) and progression-free survival (PFS) was calculated by Kaplan–Meier method. Median expression of Nectin-4 was 150 (range 0–250) in SCC, 140.5 (range 30–275) in ADENO, and 10 (0–185) in SARCO, with significantly lower levels for SARCO compared to SCC or ADENO (<i>p</i> < 0.001). For SCC, ADENO or SARCO no differences regarding OS or PFS were observed based on Nectin-4 expression levels (<i>p</i> > 0.05). Multivariate analysis revealed nodal stage as an independent prognostic factor for OS and PFS and metastases for PFS but not Nectin-4 expression. In conclusion, Nectin-4 was not prognostic in histological subtypes of BC in our study cohort. However, the high expression of Nectin-4 in SCC and ADENO might guide future treatment with novel Nectin-4-directed ADCs and provide this high-risk patient collective with a new promising therapeutic option. Testing Nectin-4 expression as a biomarker should be considered in trials with SARCO, where low Nectin-4 expression has been observed.https://www.mdpi.com/2072-6694/14/18/4411Nectin-4squamous cell carcinomaneoadjuvant therapyadjuvant therapyantibody–drug conjugate |
| spellingShingle | Severin Rodler Lennert Eismann Boris Schlenker Jozefina Casuscelli Isabel Brinkmann Andrea Sendelhofert Raphaela Waidelich Alexander Buchner Christian Stief Gerald Bastian Schulz Stephan Ledderose Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients? Cancers Nectin-4 squamous cell carcinoma neoadjuvant therapy adjuvant therapy antibody–drug conjugate |
| title | Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients? |
| title_full | Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients? |
| title_fullStr | Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients? |
| title_full_unstemmed | Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients? |
| title_short | Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients? |
| title_sort | expression of nectin 4 in variant histologies of bladder cancer and its prognostic value need for biomarker testing in high risk patients |
| topic | Nectin-4 squamous cell carcinoma neoadjuvant therapy adjuvant therapy antibody–drug conjugate |
| url | https://www.mdpi.com/2072-6694/14/18/4411 |
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