Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma
Neoadjuvant therapy (NT) for advanced PDAC is an emerging concept, affecting both stroma and tumor. The Activated Stroma Index (ASI; ratio of activated cancer-associated fibroblasts (CAF) to collagen deposition) is a prognostic marker in upfront resected pancreatic adenocarcinoma (PDAC). We assessed...
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/16/3881 |
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| author | Ulrike Heger Anna Martens Lisa Schillings Britta Walter Domenic Hartmann Ulf Hinz Thomas Pausch Nathalia Giese Christoph W. Michalski Thilo Hackert |
| author_facet | Ulrike Heger Anna Martens Lisa Schillings Britta Walter Domenic Hartmann Ulf Hinz Thomas Pausch Nathalia Giese Christoph W. Michalski Thilo Hackert |
| author_sort | Ulrike Heger |
| collection | DOAJ |
| description | Neoadjuvant therapy (NT) for advanced PDAC is an emerging concept, affecting both stroma and tumor. The Activated Stroma Index (ASI; ratio of activated cancer-associated fibroblasts (CAF) to collagen deposition) is a prognostic marker in upfront resected pancreatic adenocarcinoma (PDAC). We assessed ASI and its prognostic relevance after NT. Tissue from resection specimens of <i>n</i> = 48 PDAC patients after neoadjuvant chemotherapy with FOLFIRINOX (FOL; <i>n</i> = 31), gemcitabine + nab-paclitaxel (GEM; 7) or combination treatment (COMB; 10) was compared with upfront resected matched controls (RES; 69). Activated CAFs were assessed by immunohistochemistry for α-SMA, and collagen was stained with aniline blue; the stained area was then determined by computational imaging analysis and ASI was calculated. In GEM, ASI was significantly higher and collagen deposition lower than in controls and FOL. The lowest quartile of ASI values had significantly longer overall survival (OS) in RES, whereas in FOL, the highest quartile had the best prognosis. After NT, OS was significantly improved in the α-SMA-high group; in RES, however, survival was independent of α-SMA. Reversed prognostic association of ASI thus points to the differing significance of stromal composition after FOL, while improved prognosis with high CAF abundance suggests a synergistic effect of myofibroblasts with chemotherapy. These divergences impede usability of ASI after NT. |
| first_indexed | 2024-03-09T04:37:41Z |
| format | Article |
| id | doaj.art-159d970c4cd74448962c261a01dbe672 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:37:41Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-159d970c4cd74448962c261a01dbe6722023-12-03T13:24:37ZengMDPI AGCancers2072-66942022-08-011416388110.3390/cancers14163881Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic CarcinomaUlrike Heger0Anna Martens1Lisa Schillings2Britta Walter3Domenic Hartmann4Ulf Hinz5Thomas Pausch6Nathalia Giese7Christoph W. Michalski8Thilo Hackert9Department of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyDepartment of General Surgery, University Hospital, 89081 Ulm, GermanyDepartment of General Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, GermanyNeoadjuvant therapy (NT) for advanced PDAC is an emerging concept, affecting both stroma and tumor. The Activated Stroma Index (ASI; ratio of activated cancer-associated fibroblasts (CAF) to collagen deposition) is a prognostic marker in upfront resected pancreatic adenocarcinoma (PDAC). We assessed ASI and its prognostic relevance after NT. Tissue from resection specimens of <i>n</i> = 48 PDAC patients after neoadjuvant chemotherapy with FOLFIRINOX (FOL; <i>n</i> = 31), gemcitabine + nab-paclitaxel (GEM; 7) or combination treatment (COMB; 10) was compared with upfront resected matched controls (RES; 69). Activated CAFs were assessed by immunohistochemistry for α-SMA, and collagen was stained with aniline blue; the stained area was then determined by computational imaging analysis and ASI was calculated. In GEM, ASI was significantly higher and collagen deposition lower than in controls and FOL. The lowest quartile of ASI values had significantly longer overall survival (OS) in RES, whereas in FOL, the highest quartile had the best prognosis. After NT, OS was significantly improved in the α-SMA-high group; in RES, however, survival was independent of α-SMA. Reversed prognostic association of ASI thus points to the differing significance of stromal composition after FOL, while improved prognosis with high CAF abundance suggests a synergistic effect of myofibroblasts with chemotherapy. These divergences impede usability of ASI after NT.https://www.mdpi.com/2072-6694/14/16/3881pancreatic cancerFOLFIRINOXpaclitaxelneoadjuvant therapytumor stromaCAF |
| spellingShingle | Ulrike Heger Anna Martens Lisa Schillings Britta Walter Domenic Hartmann Ulf Hinz Thomas Pausch Nathalia Giese Christoph W. Michalski Thilo Hackert Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma Cancers pancreatic cancer FOLFIRINOX paclitaxel neoadjuvant therapy tumor stroma CAF |
| title | Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma |
| title_full | Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma |
| title_fullStr | Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma |
| title_full_unstemmed | Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma |
| title_short | Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma |
| title_sort | myofibroblastic caf density not activated stroma index indicates prognosis after neoadjuvant therapy of pancreatic carcinoma |
| topic | pancreatic cancer FOLFIRINOX paclitaxel neoadjuvant therapy tumor stroma CAF |
| url | https://www.mdpi.com/2072-6694/14/16/3881 |
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