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. Author manuscript; available in PMC: 2016 Jan 16.
Published in final edited form as: J Pathol. 2015 Oct 14;238(1):31–41. doi: 10.1002/path.4628

Figure 4.

Figure 4

Proposed model of retrograde glandular colonization. All invasive adenocarcinoma cells are ERG-positive due to an early TMPRSS2–ERG fusion event, yet only part of the invasive adenocarcinoma shows PTEN loss and is therefore considered subclonal loss. In such an ERG-positive invasive adenocarcinoma with subclonal loss of PTEN, TMPRSS2–ERG genomic breakpoint analysis establishes the shared clonal origin of lesions. Subclonal PTEN loss can be used as a temporal vector. The observation that ERG-positive PTEN-negative cells populate normal acinar and ductal structures strongly suggests a retrograde spreading pattern of invasive carcinoma cells into benign glandular structures. PTEN-proficient normal prostate epithelial cells and adenocarcinoma are shown in brown. PTEN-deficient cells are drawn in grey. ERG overexpression is indicated by blue nuclei. Intact basal cells are highlighted in red.