Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the KrasLSL-G12D/+; Trp53flox/flox lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential.

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Although adrenal glands are a common site of metastatic cancer, clinically significant haemorrhage into these is very uncommon with only a few cases having been previously published in the English literature. Here, a case of massive adrenal haemorrhage secondary to metastasis of lung cancer that led to the death of the patient is reported. To the best of our knowledge, such an acute death, without any prior medical attention or intervention, as a consequence of haemorrhagic adrenal metastasis has not been described before and is an important consideration in a person with lung cancer who dies unexpectedly.

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Hypertensive disorders associated with pregnancy (24.2%) and anemia (14.7%) were most common. In the hypertensive group, important findings were disseminated intravascular coagulation, hemorrhages in different organs and thromboemboli. Two cases were HIV seropositive. The autopsy helped to elucidate factors contributing to death and pathology in different organ systems.