The landscape of metastatic progression patterns across major human cancers.
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.
Institute of Pathology, Charité University Hospital, Berlin, Germany. German Cancer Research Center (DKFZ), Heidelberg, Germany. German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Jan
J
Budczies
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Moritz
M
von Winterfeld
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Frederick
F
Klauschen
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Michael
M
Bockmayr
Massachusetts General Hospital/Harvard Medical School, Department of Pathology, Boston, MA, USA.
Jochen K
JK
Lennerz
Institute of Pathology, Charité University Hospital, Berlin, Germany. German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Carsten
C
Denkert
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Thomas
T
Wolf
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Arne
A
Warth
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Manfred
M
Dietel
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Ioannis
I
Anagnostopoulos
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany. National Center for Tumor Diseases (NCT),Heidelberg, Germany.
Wilko
W
Weichert
Institute of Legal Medicine, University Hospital Münster, Münster, Germany.
Daniel
D
Wittschieber
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Albrecht
A
Stenzinger
D000230:Adenocarcinoma / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects