Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma
Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entit...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/22/16292 |
| _version_ | 1797458983522402304 |
|---|---|
| author | Franz Sellner Eva Compérat Martin Klimpfinger |
| author_facet | Franz Sellner Eva Compérat Martin Klimpfinger |
| author_sort | Franz Sellner |
| collection | DOAJ |
| description | Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entity surprises with additional clinical peculiarities: (a) the unusually long interval of about 9 years between the primary RCC and the onset of pancreatic metastases; (b) multiple pancreatic metastases occurring in 36% of cases; (c) favourable treatment outcomes with a 75% 5-year survival rate; and (d) volume and growth-rate dependent risk factors generally accepted to be relevant for overall survival in metastatic surgery are insignificant in isPMRCC. The genetic and epigenetic causes of exclusive pancreatic involvement have not yet been investigated and are currently unknown. Conversely, according to the few available data in the literature, the following genetic and epigenetic peculiarities can already be identified as the cause of the protracted course: 1. high genetic stability of the tumour cell clones in both the primary tumour and the pancreatic metastases; 2. a low frequency of copy number variants associated with aggressiveness, such as 9p, 14q and 4q loss; 3. in the chromatin-modifying genes, a decreased rate of <i>PAB1</i> (3%) and an increased rate of <i>PBRM1</i> (77%) defects are seen, a profile associated with a favourable course; 4. an increased incidence of <i>KDM5C</i> mutations, which, in common with increased <i>PBRM1</i> alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT. |
| first_indexed | 2024-03-09T16:45:55Z |
| format | Article |
| id | doaj.art-679aad7d9cfc4566adc5cbdafd19bdda |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:45:55Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-679aad7d9cfc4566adc5cbdafd19bdda2023-11-24T14:47:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221629210.3390/ijms242216292Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell CarcinomaFranz Sellner0Eva Compérat1Martin Klimpfinger2Department of General, Visceral and Vascular Surgery, Clinic Favoriten Vienna, Kaiser Franz Josef Hospital, 1100 Vienna, AustriaClinical Institute of Pathology, Medical University Vienna, 1090 Vienna, AustriaClinical Institute of Pathology, Medical University Vienna, 1090 Vienna, AustriaIsolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entity surprises with additional clinical peculiarities: (a) the unusually long interval of about 9 years between the primary RCC and the onset of pancreatic metastases; (b) multiple pancreatic metastases occurring in 36% of cases; (c) favourable treatment outcomes with a 75% 5-year survival rate; and (d) volume and growth-rate dependent risk factors generally accepted to be relevant for overall survival in metastatic surgery are insignificant in isPMRCC. The genetic and epigenetic causes of exclusive pancreatic involvement have not yet been investigated and are currently unknown. Conversely, according to the few available data in the literature, the following genetic and epigenetic peculiarities can already be identified as the cause of the protracted course: 1. high genetic stability of the tumour cell clones in both the primary tumour and the pancreatic metastases; 2. a low frequency of copy number variants associated with aggressiveness, such as 9p, 14q and 4q loss; 3. in the chromatin-modifying genes, a decreased rate of <i>PAB1</i> (3%) and an increased rate of <i>PBRM1</i> (77%) defects are seen, a profile associated with a favourable course; 4. an increased incidence of <i>KDM5C</i> mutations, which, in common with increased <i>PBRM1</i> alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT.https://www.mdpi.com/1422-0067/24/22/16292renal cell carcinomaisolated pancreatic metastasesgeneticsepigeneticsseed and soil mechanism |
| spellingShingle | Franz Sellner Eva Compérat Martin Klimpfinger Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma International Journal of Molecular Sciences renal cell carcinoma isolated pancreatic metastases genetics epigenetics seed and soil mechanism |
| title | Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma |
| title_full | Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma |
| title_fullStr | Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma |
| title_full_unstemmed | Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma |
| title_short | Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma |
| title_sort | genetic and epigenetic characteristics in isolated pancreatic metastases of clear cell renal cell carcinoma |
| topic | renal cell carcinoma isolated pancreatic metastases genetics epigenetics seed and soil mechanism |
| url | https://www.mdpi.com/1422-0067/24/22/16292 |
| work_keys_str_mv | AT franzsellner geneticandepigeneticcharacteristicsinisolatedpancreaticmetastasesofclearcellrenalcellcarcinoma AT evacomperat geneticandepigeneticcharacteristicsinisolatedpancreaticmetastasesofclearcellrenalcellcarcinoma AT martinklimpfinger geneticandepigeneticcharacteristicsinisolatedpancreaticmetastasesofclearcellrenalcellcarcinoma |