Histogenic analysis confirms prostate cancer metastasis to lung.

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Histogenic analysis confirms prostate cancer metastasis to lung. Histogenic analysis confirms prostate cancer metastasis to lung. A, autopsy imaging of the mock-castrated RapidCaP mouse (#3) reveals disease dissemination to lung, lymph nodes, spleen, and liver at the trial endpoint (10 months after injection). B, identification of histogenic markers that define prostate cancer cells by IHC analysis of prostate in animal from A: Pten and Ck8 (black arrows, see black arrowheads for region with normal protein levels) and Pten and AR (red arrows, see red arrowheads for the region with normal protein levels). Note that “loss” of AR staining is a hallmark of Pten/p53-null prostate (see the text). Scale bar, 100 μm. C and D, IHC analysis of lung from above mouse reveals metastatic nodules that are Pten-, Ck8-, and AR-negative and positive for the prostate epithelial marker Nkx3.1. Boxes, areas of magnification. Scale bars, 100 μm (top and bottom left) and 50 μm (all other panels). E, double immunofluorescence (IF) labeling confirms double negativity for Pten and Ck8 in a metastatic lung nodule (nod) shown in C and D (yellow circles and arrowheads). Note that, in contrast, colabeling of Pten and Ck8 in adjacent normal lung epithelia (nl, white dashed circles and arrowheads) shows double-positive staining. Scale bar, 50 μm. F, anti-luciferase antibody staining and immunofluorescence analysis of lung from C to F confirms that metastatic nodules are luciferase-positive (white arrows) and Pten/Ck8–deficient (red arrowheads). Scale bar, 100 μm. Hyejin Cho et al. Cancer Discovery 2014;4:318-333 ©2014 by American Association for Cancer Research