Fig. 2.
TMPRSS2-ERG fusion and PI3K pathway activation are cooperative events in prostate cancer. All pictures show the ventral prostate lobe. a, No PIN is noted in either wild type or TMPRSS2-ERG animals at 12 months of age (H&E, 200X). b, The proportion of human prostate cancers that show PTEN genomic loss, ERG rearrangement, both, or neither are shown (n = 121). PTEN loss was defined as having reduced copy number by RAE (heterozygous or homozygous loss; FDR q-value<6.93×10−8). ERG rearrangement was defined as the consequence of interstitial deletion by aCGH (q-value<6.93×10−8) and increased expression of ERG downstream of common translocation breakpoints (exons 5–8) relative to early ERG exons (exons 1–2) [>2 s.d. above the mean of normal samples (n=29) by exon expression array] The significance of the association between PTEN loss and ERG rearrangement is p-value<0.002 as determined by Fisher's exact test (right tail). c, The proportion of human prostate cancers that show MYC genomic amplification, ERG rearrangement, both, or neither are shown (n = 121). MYC amplification was defined as having increased copy number (q-value<1.2×10−7). ERG rearrangement and the significance of association (p-value=0.56) was defined as in Fig 2b. d, Normal prostate in Pten +/− and high grade PIN in Pten +/−; TMPRSS2-ERG mice at 6 months of age (H&E, 200X). Arrows indicate PIN and arrowheads show normal epithelium for comparison. e, Immunohistochemistry for smooth muscle actin in a Pten +/− and a Pten +/−; TMPRSS2-ERG mouse (400X). Compare disrupted and absent smooth muscle stroma around areas of possible microinvasion from a Pten +/−; TMPRSS2-ERG mouse (right column, arrows) to minimally attenuated smooth muscle sheath around area of high grade PIN in Pten +/− (left column, arrows) and to intact stroma of normal glands in both animals. f, Low grade PIN in AKT transgenic mice and high grade PIN in AKT; TMPRSS2-ERG double transgenic animals at 11 months of age (H&E, 400X). Arrows indicate PIN and arrowheads show normal epithelium for comparison.
