Vasculogenic mimicry (VM) is the formation of vascular channels lacking endothelial cells. These channels are lined by tumor cells with cancer stem cell features, positive for periodic acid-Schiff, and negative for CD31 staining. The term VM was introduced by Maniotis et al. (1), who reported this phenomenon in highly aggressive uveal melanomas; since then, VM has been associated with poor prognosis, tumor aggressiveness, metastasis, and drug resistance in several tumors, including breast cancer. It is proposed that VM and angiogenesis (the de novo formation of blood vessels from the established vasculature by endothelial cells, which is observed in several tumors) rely on some common mechanisms. Furthermore, it is also suggested that VM could constitute a means to circumvent anti-angiogenic treatment in cancer. Therefore, it is important to determinant the factors that dictate the onset of VM. In this review, we describe the current understanding of VM formation in breast cancer, including specific signaling pathways, and cancer stem cells. In addition, we discuss the clinical significance of VM in prognosis and new opportunities of VM as a target for breast cancer therapy.

Hepatocellular carcinoma (HCC) has very poor prognosis. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including the Eag1 (ether à-go-go-1) potassium channel that is overexpressed in human HCC. Eag1 channels are regulated by cancer etiological factors and have been proposed as early tumor markers. Here, we found that HepG2 and HuH-7 HCC cells displayed Eag1 messenger RNA (mRNA) and protein expression, determined by real-time RT-PCR and immunochemistry, respectively. Astemizole inhibited human HCC cell proliferation (assessed by metabolic activity assay) and induced apoptosis (studied with flow cytometry) in both cell lines. The subcellular Eag1 protein localization was modified by astemizole in the HepG2 cells. The treatment with astemizole prevented diethylnitrosamine (DEN)-induced rat HCC development in vivo (followed by studying γ-glutamyl transpeptidase (GGT) activity). The Eag1 mRNA and protein levels were increased in most DEN-treated groups but decreased after astemizole treatment. GGT activity was decreased by astemizole. The Eag1 protein was detected in cirrhotic and dysplastic rat livers. Astemizole might have clinical utility for HCC prevention and treatment, and Eag1 channels may be potential early HCC biomarkers. These data provide significant basis to include astemizole in HCC clinical trials.

In certain myofibroblastic lesions, the use of auxiliary techniques (such as immunohistochemistry) can be critical for differential diagnosis.

Lung cancer (LC) is the first cause of cancer-related deaths worldwide. Elucidating the pathogenesis of LC will give information on key elements of tumor initiation and development while helping to design novel targeted therapies. LC is an heterogeneous disease that has the second highest mutation rate surpassed only by melanoma, since 90% of LC occurs in tobacco smokers. However, only a small percent of smokers develops LC, indicating an inherent genomic instability. Additionally, LC in never smokers suggests other molecular mechanisms not causally linked to tobacco carcinogens. This review presents a current outlook of the connection between LC and genomic instability at the molecular and clinical level summarizing its implications for diagnosis, therapy, and prognosis. The genomic landscape of LC shows widespread alterations such as DNA methylation, point mutations, copy number variation, chromosomal translocations, and aneuploidy. Genome maintenance mechanisms including cell cycle control, DNA repair, and mitotic checkpoints open a window to translational research for finding novel diagnostic biomarkers and targeted therapies in LC.

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The histopathologist should be aware of the possibility of MPC. Three-year survival is worse than in patients with conventional colonic carcinomas in Stage III.

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