The landscape of metastatic progression patterns across major human cancers

// Jan Budczies 1,2,6,* , Moritz von Winterfeld 1,* , Frederick Klauschen 1 , Michael Bockmayr 1 , Jochen K. Lennerz 3 , Carsten Denkert 1,6 , Thomas Wolf 4,6 , Arne Warth 4 , Manfred Dietel 1 , Ioannis Anagnostopoulos 1 , Wilko Weichert 4,6,7 , Daniel Wittschieber 5 and Albrecht Stenzinger 4 1 Institute of Pathology, Charité University Hospital, Berlin, Germany 2 German Cancer Research Center (DKFZ), Heidelberg, Germany 3 Massachusetts General Hospital/Harvard Medical School, Department of Pathology, Boston, MA, USA 4 Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany 5 Institute of Legal Medicine, University Hospital Münster, Münster, Germany 6 German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany 7 National Center for Tumor Diseases (NCT),Heidelberg, Germany * These authors contributed equally to this work Correspondence: Albrecht Stenzinger, email: // Jan Budczies, email: // Keywords : autopsy, metastasis, systemic disease, carcinoma, solid tumor, cancer, survival Received : August 22, 2014 Accepted : November 04, 2014 Published : November 04, 2014 Abstract The majority of patients with solid malignancies die from metastatic burden. However, our current understanding of the mechanisms and resulting patterns of dissemination is limited. Here, we analyzed patterns of metastatic progression across 16 major cancer types in a cohort of 1008 patients with metastatic cancer autopsied between 2000 and 2013 to assess cancer specific progression patterns of disease and related risk predictions. The frequency and location of metastases were evaluated in and across 1) 16 major cancers, 2) smoking- and non-smoking-related cancers and 3) adeno- and squamous cell carcinoma. Associations between primary and secondary sites were analyzed by the fractional and the relative risk methods. We detected significantly different cancer specific patterns of metastatic progression with specific relative risk profiles for secondary site involvement. Histology and smoking etiology influenced these patterns. Backward analysis showed that metastatic patterns help to predict unknown primary sites. Solid malignancies maintain a unique and recurrent organ tropism to specific secondary sites which does not appear to be strongly influenced by advances in cancer medicine as shown by comparison with previous data sets. The delineated landscape of metastatic progression patterns is a comprehensive data resource to both clinical and basic scientists which aids fostering new hypotheses for cancer research and cancer therapies.