An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
Abstract Background Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10949-5 |
| _version_ | 1797827489532215296 |
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| author | Yosuke Yamada Ronald Simon Kosuke Iwane Yuki Nakanishi Yasuhide Takeuchi Akihiko Yoshizawa Masahiro Takada Masakazu Toi Hironori Haga Alexander Marx Guido Sauter |
| author_facet | Yosuke Yamada Ronald Simon Kosuke Iwane Yuki Nakanishi Yasuhide Takeuchi Akihiko Yoshizawa Masahiro Takada Masakazu Toi Hironori Haga Alexander Marx Guido Sauter |
| author_sort | Yosuke Yamada |
| collection | DOAJ |
| description | Abstract Background Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ. Methods Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells. Results Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the “master regulator” of TNBCs. Conclusions POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs. |
| first_indexed | 2024-04-09T12:49:08Z |
| format | Article |
| id | doaj.art-225b014910d4434f9d384100f9d89699 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T12:49:08Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-225b014910d4434f9d384100f9d896992023-05-14T11:19:43ZengBMCBMC Cancer1471-24072023-05-0123111110.1186/s12885-023-10949-5An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9Yosuke Yamada0Ronald Simon1Kosuke Iwane2Yuki Nakanishi3Yasuhide Takeuchi4Akihiko Yoshizawa5Masahiro Takada6Masakazu Toi7Hironori Haga8Alexander Marx9Guido Sauter10Department of Diagnostic Pathology, Kyoto University HospitalInstitute of Pathology, University Medical Center Hamburg-EppendorfDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of MedicineDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Breast Surgery, Kyoto University Graduate School of MedicineDepartment of Breast Surgery, Kyoto University Graduate School of MedicineDepartment of Diagnostic Pathology, Kyoto University HospitalInstitute of Pathology, Mannheim and Medical Faculty Mannheim, University Medical Centre, Heidelberg UniversityInstitute of Pathology, University Medical Center Hamburg-EppendorfAbstract Background Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ. Methods Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells. Results Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the “master regulator” of TNBCs. Conclusions POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs.https://doi.org/10.1186/s12885-023-10949-5Breast neoplasmsPOU2F3SOX9Triple-negative breast neoplasmsTuft cells |
| spellingShingle | Yosuke Yamada Ronald Simon Kosuke Iwane Yuki Nakanishi Yasuhide Takeuchi Akihiko Yoshizawa Masahiro Takada Masakazu Toi Hironori Haga Alexander Marx Guido Sauter An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 BMC Cancer Breast neoplasms POU2F3 SOX9 Triple-negative breast neoplasms Tuft cells |
| title | An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 |
| title_full | An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 |
| title_fullStr | An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 |
| title_full_unstemmed | An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 |
| title_short | An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 |
| title_sort | exploratory study for tuft cells in the breast and their relevance in triple negative breast cancer the possible relationship of sox9 |
| topic | Breast neoplasms POU2F3 SOX9 Triple-negative breast neoplasms Tuft cells |
| url | https://doi.org/10.1186/s12885-023-10949-5 |
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