Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study
Abstract Background Microsatellite instability (MSI) and deficiency in the human mismatch repair (MMR) system are critical drivers of genomic instability in various cancers. Tumors exhibiting MSI and MMR deficiency (dMMR) have prognostic implications and are associated with differential responses to...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-05-01
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| Series: | Journal of the Egyptian National Cancer Institute |
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| Online Access: | https://doi.org/10.1186/s43046-025-00279-x |
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| author | Ahlem Bdioui Mariem Akkari Maroua Krifa Yosra Souiden Ethmane Sleimane Wafa Mokni Nada Ben Lazrek Sarra Mestiri Sihem Hmissa Nabiha Missaoui |
| author_facet | Ahlem Bdioui Mariem Akkari Maroua Krifa Yosra Souiden Ethmane Sleimane Wafa Mokni Nada Ben Lazrek Sarra Mestiri Sihem Hmissa Nabiha Missaoui |
| author_sort | Ahlem Bdioui |
| collection | DOAJ |
| description | Abstract Background Microsatellite instability (MSI) and deficiency in the human mismatch repair (MMR) system are critical drivers of genomic instability in various cancers. Tumors exhibiting MSI and MMR deficiency (dMMR) have prognostic implications and are associated with differential responses to immune checkpoint inhibitors. Given their key roles in tumorigenesis, investigating MMR protein expression and MSI in urothelial cancer of the bladder is essential to improve therapeutic strategies and deepen understanding of its molecular features. This study aimed to assess MMR protein expression and MSI in primary urothelial carcinoma of the bladder and to evaluate their associations with clinicopathological characteristics. Methods A total of 49 primary urothelial carcinomas were analyzed for MMR expression using immunohistochemistry, and dMMR tumors underwent further analysis for MSI status using the markers of the Bethesda panel (BAT25, BAT26, D2S123, D5S346, and D17S250). The MMR expression and MSI findings were associated with clinicopathological parameters. Results dMMR was identified in two high-grade urothelial carcinomas (4.1%), while the remaining cases demonstrated proficient MMR. Both dMMR tumors showed impaired immunoreactivity, with one tumor displaying a simultaneous loss of the MLH1/PMS2 heterodimer and the other showing isolated MSH6 loss. MSI analysis revealed instability in BAT26 in the MLH1/PMS2-deficient tumor and at D17S250 in the MSH6-deficient tumor. Both tumors exhibited low-level MSI (MSI-L). No relevant associations were found between MMR/MSI status and clinicopathological features (p > 0.05). Conclusions The identification of MSI-L and MMR deficiency in only two samples underscores the rarity of MSI in urothelial carcinoma among Tunisian patients. These findings emphasize the need for larger, multi-center studies to elucidate the MSI/dMMR molecular and clinical implications in bladder carcinoma. |
| format | Article |
| id | doaj-art-ccb2059b62164cf2bbe17cbf6af245cb |
| institution | OA Journals |
| issn | 2589-0409 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | SpringerOpen |
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| series | Journal of the Egyptian National Cancer Institute |
| spelling | doaj-art-ccb2059b62164cf2bbe17cbf6af245cb2025-08-20T02:03:38ZengSpringerOpenJournal of the Egyptian National Cancer Institute2589-04092025-05-013711910.1186/s43046-025-00279-xMicrosatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center studyAhlem Bdioui0Mariem Akkari1Maroua Krifa2Yosra Souiden3Ethmane Sleimane4Wafa Mokni5Nada Ben Lazrek6Sarra Mestiri7Sihem Hmissa8Nabiha Missaoui9Research Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SoussePathology Department, Farhet Hached University HospitalPathology Department, Sahloul University HospitalResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseResearch Laboratory Lr21es03, Oncogenesis and Tumor Progression, Medicine Faculty of Sousse, University of SousseAbstract Background Microsatellite instability (MSI) and deficiency in the human mismatch repair (MMR) system are critical drivers of genomic instability in various cancers. Tumors exhibiting MSI and MMR deficiency (dMMR) have prognostic implications and are associated with differential responses to immune checkpoint inhibitors. Given their key roles in tumorigenesis, investigating MMR protein expression and MSI in urothelial cancer of the bladder is essential to improve therapeutic strategies and deepen understanding of its molecular features. This study aimed to assess MMR protein expression and MSI in primary urothelial carcinoma of the bladder and to evaluate their associations with clinicopathological characteristics. Methods A total of 49 primary urothelial carcinomas were analyzed for MMR expression using immunohistochemistry, and dMMR tumors underwent further analysis for MSI status using the markers of the Bethesda panel (BAT25, BAT26, D2S123, D5S346, and D17S250). The MMR expression and MSI findings were associated with clinicopathological parameters. Results dMMR was identified in two high-grade urothelial carcinomas (4.1%), while the remaining cases demonstrated proficient MMR. Both dMMR tumors showed impaired immunoreactivity, with one tumor displaying a simultaneous loss of the MLH1/PMS2 heterodimer and the other showing isolated MSH6 loss. MSI analysis revealed instability in BAT26 in the MLH1/PMS2-deficient tumor and at D17S250 in the MSH6-deficient tumor. Both tumors exhibited low-level MSI (MSI-L). No relevant associations were found between MMR/MSI status and clinicopathological features (p > 0.05). Conclusions The identification of MSI-L and MMR deficiency in only two samples underscores the rarity of MSI in urothelial carcinoma among Tunisian patients. These findings emphasize the need for larger, multi-center studies to elucidate the MSI/dMMR molecular and clinical implications in bladder carcinoma.https://doi.org/10.1186/s43046-025-00279-xUrothelial carcinomaBladderDMMRMSIImmunohistochemistryPCR |
| spellingShingle | Ahlem Bdioui Mariem Akkari Maroua Krifa Yosra Souiden Ethmane Sleimane Wafa Mokni Nada Ben Lazrek Sarra Mestiri Sihem Hmissa Nabiha Missaoui Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study Journal of the Egyptian National Cancer Institute Urothelial carcinoma Bladder DMMR MSI Immunohistochemistry PCR |
| title | Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study |
| title_full | Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study |
| title_fullStr | Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study |
| title_full_unstemmed | Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study |
| title_short | Microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma: a Tunisian single-center study |
| title_sort | microsatellite instability and mismatch repair deficiency in bladder urothelial carcinoma a tunisian single center study |
| topic | Urothelial carcinoma Bladder DMMR MSI Immunohistochemistry PCR |
| url | https://doi.org/10.1186/s43046-025-00279-x |
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