Pancreatic metastases from kidney cancer are rare and intriguing. Typically, when kidney cancer spreads, it affects multiple organs, but in these uncommon cases, it only affects the pancreas. Even more surprising is that these metastases often appear many years—sometimes nearly a decade—after the initial diagnosis of kidney cancer and the surprisingly favourable surgical and drug treatment results. This unusual pattern of cancer spread raises important questions about the genetic and biological factors that may explain such unique behavior.
Researchers, led by Professor Franz Sellner from the Kaiser Franz Josef Hospital, together with Professor Eva Compérat and Professor Martin Klimpfinger from the Medical University of Vienna, conducted a comprehensive review of existing research on isolated pancreatic metastases from clear-cell kidney cancer. This work provides an overview and analysis of the limited studies published so far on this rare form of metastasis. Their review was published in the International Journal of Molecular Sciences.
A key observation from the review is the frequent occurrence of changes in the PBRM1 gene, which have been linked to better outcomes for patients. Professor Sellner explained, “The results of our analysis suggest that genetic factors, like higher levels of PBRM1 mutations and fewer PAB1 mutations, may contribute to the less aggressive nature of pancreatic metastases when compared to other sites.” However, they stressed that these conclusions must be viewed cautiously due to the small number of cases available for study.
The review also examined the broader genetic and epigenetic factors (e.g. genetic profile, reduced DNA methylation in certain genes and altered microRNA activity) in RCC that might play a part in how cancers spreads and grows in the pancreas. As the authors point out, the isPMRCC showed an independent genetic profile characterized by a low frequency of copy number variants associated with aggressiveness like 9p, 14q and 4q loss, and a low genetic instability index. Furthermore, the pancreatic metastases of clear cell renal carcinoma do not belong to an inflammatory but to angiogenetic subtype. This behaviour, in turn, confirms the limited clinical data of a good response to antiangiogenic therapy in the absence of response to IT. This type of tumour is also developing into personalized therapies, where doctors tailor therapies based on an individual’s genetic/epigenetic makeup, are important in managing these unique pancreatic metastases.
Their review also supports the “seed and soil” idea, which proposes that some cancers tend to spread to specific organs because of favorable conditions in those tissues. In this case, the pancreas may offer an environment where genetically stable cancer cells can grow more easily. “This theory provides insight into why the pancreas might be more likely to attract these metastases, but more research is needed to fully understand the underlying reasons,” Professor Sellner commented.
Overall, the review by Professor Sellner, Professor Compérat, and Professor Klimpfinger offers valuable insights into the genetic and biological traits of isolated pancreatic metastases from clear-cell kidney cancer. The researchers emphasize that these findings should be interpreted with care, as the number of cases is still small and more research is necessary. Their work paves the way for future studies that could lead to better, more personalized treatments for this rare form of cancer, and may be one day help us therapeutically reduce the metastatic potential of tumours.
Journal Reference
Sellner, F., Compérat, E., & Klimpfinger, M. “Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma.” Int. J. Mol. Sci. 2023, 24, 16292. DOI: https://doi.org/10.3390/ijms242216292
About the Authors
Prof. Franz Sellner received his MD at the University of Vienna in 1971. Starting in 1973, he received specialist training for surgery at Kaiser Franz Josef Hospital Vienna, and from 1980 until his retirement in 2008, he was a specialist in surgery at the Dept. of Surgery, Kaiser Franz Josef Hospital. In 2008, he was awarded the title “University Professor” of Surgery at the Medical University of Vienna. He has published 145 research works with 1330 citations and 2135 reads, in the fields of: adenoma-carcinoma-sequence in the small bowel; epidemiology and surgical management of periampullary and pancreatic tumours; and epidemiology and arguments for the impact of a “Seed and Soil Mechanism” in isolated pancreatic metastasis of renal cell carcinoma.
Prof. Eva Compérat is Head of the Department of Pathology at the L’Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, in Paris, France and consulting pathologist specializing in muscle-invasive and non-muscle-invasive bladder cancer and penile carcinoma for the European Association of Urology (EAU). She is also a member of several notable international societies in uropathology including the EAU, the International Society of Urological Pathology, and the Genitourinary Pathology Society. She serves (or has served) on the editorial boards of journals including the World Journal of Urology, Pathology, and European Urology Oncology, and is recognized as co-author of WHO Tumours of the Urinary System and Male Genital Organs (4th ed.) and editorial member of the 5th ed. She is equally dedicated to educational efforts in her specialized field (she has held a teaching position at the Université Pierre et Marie Curie in Paris since 2002) and is a frequent contributor to educational exchanges of the International Academy of Pathology. She is current Austrian affiliation in the Department of Pathology at the Medical University of Vienna.
Prof. Martin Klimpfinger studied medicine at the Medical Faculty of the Karl Franzens University (KFU) in Graz (since 2004: Medical University of Graz), where he received his doctorate in 1983. He is an Austrian pathologist and university professor. He was head of the Pathological-Bacteriological Institute of the Sozialmedizinisches Zentrum Süd—Klinik Favoriten, the former Kaiser Franz Josef-Spital, an academic teaching hospital of the Medical University of Vienna, from 1997 to 2020. He was also President from 2015 to 2016 and Past-President from 2017 to 2018 of the Austrian Society of Clinical Pathology and Molecular Pathology, formerly the Austrian Society of Pathology – Austrian Division of the International Academy of Pathology. Currently, he is responsible for public relations as a board member of the society since 2019.
