Figure 3.

(a) Frequency of prostate cancer lesions in Min and Rag-deficient Min mice. Depletion of CD25⁺ cells (Min⁺anti-CD25) (N = 8 mice per trial) accelerated prostate carcinogenesis at age of 3 months, and the frequency of HGPIN and microinvasive adenocarcinoma was significantly higher than those of age-matched (N = 5 mice per trial) or sham-treated (N = 8) mice (p < 0.01 and <0.05, respectively). Compared to the age-matched Min mice (N = 5), RagMin mice (N = 8) had significantly higher frequency of prostate neoplasia at 6 months old (p < 0.05). Assays used tissues from 5 to 8 mice per treatment group (as shown) with review of microscopic fields as described in Material and methods. (b) Histology of dorsolateral prostate illustrating selected key intermediate steps in progression of carcinogenesis in Apc^Min/+ mice. (a) Normal-appearing prostate gland. (b) Low-grade prostatic intraepithelial neoplasia (PIN) with epithelial tufting and nuclear stratification. Cellular atypia is evidenced by the presence of nuclear enlargement, increased but not severe nuclear pleomorphism, hyperchromasia and occasional prominent nucleoli. (c) High-grade PIN. Note the irregular contour of the prostate gland. Highly atypical cells with severe nuclear pleomorphism and hyperchromasia fill the lumen. (d) Microinvasive carcinoma. Epithelial cells with notably large, euchromatinic nuclei bearing prominently enlarged nucleoli with penetration through the basement membrane into surrounding stroma. (e) Invasive adenocarcinoma. Moderately differentiated small, irregular malignant glands are bounded by desmoplastic stroma. Hematoxylin and Eosin. Bars: 25 µm. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]