The landscape of metastatic progression patterns across major human cancers

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.

An in vivo multiplexed small-molecule screening platform

“…These variants can each be pretreated with a single compound in vitro , pooled, injected intravenously into recipient mice, and isolated from the lungs after metastatic seeding. The lung represents one of the major metastatic sites for many cancer types including PDAC 18,24 . Determining the barcode representation by sequencing pre-injection and post-seeding samples allows parallel quantification of the effect of each treatment on metastatic seeding ability (Fig.…”

Metastatic colonization by circulating tumour cells

“…The composition of the vascular walls differs between organs and thus also influences where cancer cells extravasate (Figure 1). The capillaries in the liver and bone marrow, called sinusoids, are lined with fenestrated endothelial cells and a discontinuous basal lamina 37 , gaps that may facilitate the extravasation of CTCs and contribute to the high incidence of liver and bone metastasis 13,38 . In contrast, the endothelium of lung capillaries has tight junctions and a basement membrane, and brain capillary walls are additionally reinforced by pericytes and astrocyte processes, together constituting the blood-brain-barrier 13,37 .…”

Forearm Metastases as Unsuspected First Manifestations of Lung Adenocarcinoma

“…Most common metastatic locations are lungs, lymph nodes, liver, brain and bones, whilst other metastatic sites, like muscles, are rare and more often found during disease evolution [2]. Here we describe a clinical case of a patient diagnosed of a muscular metastases on left forearm as first clinical sign of a lung adenocarcinoma.…”