Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy
Abstract Distinct molecular subtypes of muscle‐invasive bladder cancer (MIBC) may show different platinum sensitivities. Currently available data were mostly generated at transcriptome level and have limited comparability to each other. We aimed to determine the platinum sensitivity of molecular sub...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2056-4538.70017 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832583866006634496 |
|---|---|
| author | Csilla Olah Oleksandr Shmorhun Gilbert Georg Klamminger Josefine Rawitzer Lara Sichward Boris Hadaschik Mulham Al‐Nader Ulrich Krafft Christian Niedworok Melinda Váradi Peter Nyirady Andras Kiss Eszter Szekely Henning Reis Tibor Szarvas |
| author_facet | Csilla Olah Oleksandr Shmorhun Gilbert Georg Klamminger Josefine Rawitzer Lara Sichward Boris Hadaschik Mulham Al‐Nader Ulrich Krafft Christian Niedworok Melinda Váradi Peter Nyirady Andras Kiss Eszter Szekely Henning Reis Tibor Szarvas |
| author_sort | Csilla Olah |
| collection | DOAJ |
| description | Abstract Distinct molecular subtypes of muscle‐invasive bladder cancer (MIBC) may show different platinum sensitivities. Currently available data were mostly generated at transcriptome level and have limited comparability to each other. We aimed to determine the platinum sensitivity of molecular subtypes by using the protein expression‐based Lund Taxonomy. In addition, we assessed the tumor heterogeneity within the primary tumor and between the primary and lymph node (LN) metastatic sites. Thirteen immunohistochemical markers were stained in a tissue microarray with an overall number of 1,508 cores. Statistical evaluation was performed in 199 patients divided into three chemo‐naïve MIBC cohorts: (1) pT3/4 and/or LN+ patients who received radical cystectomy without platinum treatment, (2) patients who received adjuvant chemotherapy (AC), and (3) patients who underwent palliative platinum treatment for metastatic disease or postoperative progression. Overall survival (OS) was used as the primary endpoint. Patients with the genomically unstable (GU) subtype had significantly better OS in the AC group compared to the radical cystectomy group (HR: 0.395, 95% CI: 0.205–0.795, p = 0.005). In contrast, no such association was observed for the basal/squamous (Ba/Sq) subtype. Intratumor heterogeneity was present in 19% of cases, with the lowest level in the Ba/Sq and GU tumors (14% each) and the highest level of 43% in small‐cell/neuroendocrine‐like tumors. There was greater subtype heterogeneity between primary tumors and LN metastases. In conclusion, immunohistochemistry‐based Lund Taxonomy subtypes remain stable within the same primary tumor, with the GU subtype deriving the greatest OS benefit from AC. However, high tumor heterogeneity between the primary tumor and metastatic sites can impact the effectiveness of therapies. |
| format | Article |
| id | doaj-art-c532fa1f588946c3ba9844e06c04a272 |
| institution | Kabale University |
| issn | 2056-4538 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj-art-c532fa1f588946c3ba9844e06c04a2722025-01-28T03:40:31ZengWileyThe Journal of Pathology: Clinical Research2056-45382025-01-01111n/an/a10.1002/2056-4538.70017Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapyCsilla Olah0Oleksandr Shmorhun1Gilbert Georg Klamminger2Josefine Rawitzer3Lara Sichward4Boris Hadaschik5Mulham Al‐Nader6Ulrich Krafft7Christian Niedworok8Melinda Váradi9Peter Nyirady10Andras Kiss11Eszter Szekely12Henning Reis13Tibor Szarvas14Department of Urology University of Duisburg‐Essen Essen GermanyDr. Senckenberg Institute of Pathology University Hospital Frankfurt, Goethe University Frankfurt Frankfurt am Main GermanyDr. Senckenberg Institute of Pathology University Hospital Frankfurt, Goethe University Frankfurt Frankfurt am Main GermanyInstitute of Pathology University Medicine Essen, University of Duisburg‐Essen Essen GermanyInstitute of Pathology University Medicine Essen, University of Duisburg‐Essen Essen GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyDepartment of Urology Semmelweis University Budapest HungaryDepartment of Urology Semmelweis University Budapest HungaryDepartment of Pathology, Forensic and Insurance Medicine Semmelweis University Budapest HungaryDepartment of Pathology, Forensic and Insurance Medicine Semmelweis University Budapest HungaryDr. Senckenberg Institute of Pathology University Hospital Frankfurt, Goethe University Frankfurt Frankfurt am Main GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyAbstract Distinct molecular subtypes of muscle‐invasive bladder cancer (MIBC) may show different platinum sensitivities. Currently available data were mostly generated at transcriptome level and have limited comparability to each other. We aimed to determine the platinum sensitivity of molecular subtypes by using the protein expression‐based Lund Taxonomy. In addition, we assessed the tumor heterogeneity within the primary tumor and between the primary and lymph node (LN) metastatic sites. Thirteen immunohistochemical markers were stained in a tissue microarray with an overall number of 1,508 cores. Statistical evaluation was performed in 199 patients divided into three chemo‐naïve MIBC cohorts: (1) pT3/4 and/or LN+ patients who received radical cystectomy without platinum treatment, (2) patients who received adjuvant chemotherapy (AC), and (3) patients who underwent palliative platinum treatment for metastatic disease or postoperative progression. Overall survival (OS) was used as the primary endpoint. Patients with the genomically unstable (GU) subtype had significantly better OS in the AC group compared to the radical cystectomy group (HR: 0.395, 95% CI: 0.205–0.795, p = 0.005). In contrast, no such association was observed for the basal/squamous (Ba/Sq) subtype. Intratumor heterogeneity was present in 19% of cases, with the lowest level in the Ba/Sq and GU tumors (14% each) and the highest level of 43% in small‐cell/neuroendocrine‐like tumors. There was greater subtype heterogeneity between primary tumors and LN metastases. In conclusion, immunohistochemistry‐based Lund Taxonomy subtypes remain stable within the same primary tumor, with the GU subtype deriving the greatest OS benefit from AC. However, high tumor heterogeneity between the primary tumor and metastatic sites can impact the effectiveness of therapies.https://doi.org/10.1002/2056-4538.70017bladder cancermolecular subtype classificationcisplatinchemotherapyimmunohistochemistryLund Taxonomy |
| spellingShingle | Csilla Olah Oleksandr Shmorhun Gilbert Georg Klamminger Josefine Rawitzer Lara Sichward Boris Hadaschik Mulham Al‐Nader Ulrich Krafft Christian Niedworok Melinda Váradi Peter Nyirady Andras Kiss Eszter Szekely Henning Reis Tibor Szarvas Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy The Journal of Pathology: Clinical Research bladder cancer molecular subtype classification cisplatin chemotherapy immunohistochemistry Lund Taxonomy |
| title | Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy |
| title_full | Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy |
| title_fullStr | Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy |
| title_full_unstemmed | Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy |
| title_short | Immunohistochemistry‐based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy |
| title_sort | immunohistochemistry based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy |
| topic | bladder cancer molecular subtype classification cisplatin chemotherapy immunohistochemistry Lund Taxonomy |
| url | https://doi.org/10.1002/2056-4538.70017 |
| work_keys_str_mv | AT csillaolah immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT oleksandrshmorhun immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT gilbertgeorgklamminger immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT josefinerawitzer immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT larasichward immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT borishadaschik immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT mulhamalnader immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT ulrichkrafft immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT christianniedworok immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT melindavaradi immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT peternyirady immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT andraskiss immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT eszterszekely immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT henningreis immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy AT tiborszarvas immunohistochemistrybasedmolecularsubtypesofurothelialcarcinomaderivedifferentsurvivalbenefitfromplatinumchemotherapy |