Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head
Background: Survival of patients with adenocarcinoma of the pancreas (PDAC) is poor and has remained almost unchanged over the past decades. The genomic landscape of PDAC has been characterized in recent years. The aim of this study was to identify a genetic profile as a possible predictor of prolon...
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/850 |
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| author | Sami-Alexander Safi Lena Haeberle Wolfgang Goering Verena Keitel Georg Fluegen Nikolas Stoecklein Alexander Rehders Wolfram Trudo Knoefel Irene Esposito |
| author_facet | Sami-Alexander Safi Lena Haeberle Wolfgang Goering Verena Keitel Georg Fluegen Nikolas Stoecklein Alexander Rehders Wolfram Trudo Knoefel Irene Esposito |
| author_sort | Sami-Alexander Safi |
| collection | DOAJ |
| description | Background: Survival of patients with adenocarcinoma of the pancreas (PDAC) is poor and has remained almost unchanged over the past decades. The genomic landscape of PDAC has been characterized in recent years. The aim of this study was to identify a genetic profile as a possible predictor of prolonged survival in order to tailor therapy for PDAC patients. Methods: Panel next generation sequencing (NGS) and immunohistochemistry (IHC) were performed on paraffin-embedded tumor tissues from curatively treated PDAC patients. Tumor slides were re-evaluated with a focus on the histomorphology. Patients were subgrouped according to short and long overall (<4 years/>4 years) and disease-free (<2 years/>2 years) survival. Results: Thirty-nine patients were included in the study. Clinicopathological staging variables as well as the histomorphological subgroups were homogenously distributed between short- and long-term overall and disease-free survivors. In survival analysis, patients with the <i>KRAS</i> G12D mutation and patients with <i>TP53</i> nonsense and splice-site mutations had a significantly worse overall survival (OS) and disease-free survival (DFS). Patients with long-term OS and DFS showed no <i>KRAS</i> G12D, no <i>TP53</i> nonsense or splice-site mutations. Rare Q61H/D57N <i>KRAS</i> mutations were only found in long-term survivors. The allele frequency rate of <i>KRAS</i> and <i>TP53</i> mutations in tumor cells was significantly higher in short-term disease-free survivors and overall survivors, respectively. Conclusions: NGS of PDAC revealed significant differences in survival outcome in a patient collective with homogenously distributed clinicopathological variables. Further multi-institutional studies are warranted to identify more long-term survivors to detect genetic differences suitable for targeted therapy. |
| first_indexed | 2024-03-10T00:05:05Z |
| format | Article |
| id | doaj.art-342c191da7864a54a1a7ff9aa4e56b33 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:05:05Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-342c191da7864a54a1a7ff9aa4e56b332023-11-23T16:09:42ZengMDPI AGCancers2072-66942022-02-0114385010.3390/cancers14030850Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic HeadSami-Alexander Safi0Lena Haeberle1Wolfgang Goering2Verena Keitel3Georg Fluegen4Nikolas Stoecklein5Alexander Rehders6Wolfram Trudo Knoefel7Irene Esposito8Department of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, GermanyInstitute of Pathology, Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, GermanyDepartment of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Surgery (A), Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, GermanyInstitute of Pathology, Medical Faculty, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, GermanyBackground: Survival of patients with adenocarcinoma of the pancreas (PDAC) is poor and has remained almost unchanged over the past decades. The genomic landscape of PDAC has been characterized in recent years. The aim of this study was to identify a genetic profile as a possible predictor of prolonged survival in order to tailor therapy for PDAC patients. Methods: Panel next generation sequencing (NGS) and immunohistochemistry (IHC) were performed on paraffin-embedded tumor tissues from curatively treated PDAC patients. Tumor slides were re-evaluated with a focus on the histomorphology. Patients were subgrouped according to short and long overall (<4 years/>4 years) and disease-free (<2 years/>2 years) survival. Results: Thirty-nine patients were included in the study. Clinicopathological staging variables as well as the histomorphological subgroups were homogenously distributed between short- and long-term overall and disease-free survivors. In survival analysis, patients with the <i>KRAS</i> G12D mutation and patients with <i>TP53</i> nonsense and splice-site mutations had a significantly worse overall survival (OS) and disease-free survival (DFS). Patients with long-term OS and DFS showed no <i>KRAS</i> G12D, no <i>TP53</i> nonsense or splice-site mutations. Rare Q61H/D57N <i>KRAS</i> mutations were only found in long-term survivors. The allele frequency rate of <i>KRAS</i> and <i>TP53</i> mutations in tumor cells was significantly higher in short-term disease-free survivors and overall survivors, respectively. Conclusions: NGS of PDAC revealed significant differences in survival outcome in a patient collective with homogenously distributed clinicopathological variables. Further multi-institutional studies are warranted to identify more long-term survivors to detect genetic differences suitable for targeted therapy.https://www.mdpi.com/2072-6694/14/3/850NGSKRASTP53PDACpancreatic cancermutation |
| spellingShingle | Sami-Alexander Safi Lena Haeberle Wolfgang Goering Verena Keitel Georg Fluegen Nikolas Stoecklein Alexander Rehders Wolfram Trudo Knoefel Irene Esposito Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head Cancers NGS KRAS TP53 PDAC pancreatic cancer mutation |
| title | Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head |
| title_full | Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head |
| title_fullStr | Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head |
| title_full_unstemmed | Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head |
| title_short | Genetic Alterations Predict Long-Term Survival in Ductal Adenocarcinoma of the Pancreatic Head |
| title_sort | genetic alterations predict long term survival in ductal adenocarcinoma of the pancreatic head |
| topic | NGS KRAS TP53 PDAC pancreatic cancer mutation |
| url | https://www.mdpi.com/2072-6694/14/3/850 |
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