Computerized static DNA ploidy analysis of prostatic intraepithelial neoplasia

The microscopic features of prostatic intraepithelial neoplasia (PIN) are said to identify a precursor of prostatic adenocarcinoma (PC). We investigated this sequence of neoplastic progression by studying the relationship of PIN and PC by static ploidy analysis so that PIN and PC nuclei could be distinguished morphologically from each other and separately analyzed. From 51 archival cases of PC with coexistent high-grade PIN (PIN grades II and III) 50 control nuclei, 100 PIN nuclei, and 100 carcinoma nuclei per case were identified and digitized in corresponding Feulgen-stained slides. Control and PIN ploidy histograms fit a log-normal distribution, whereas malignant nuclei fit a rectangular distribution. When the histogram patterns were classified, the incidence of aneuploidy was 25% in PIN and 41% in PC. By case, the concordance of ploidy between PIN and PC was heterogeneous, yet the DNA ploidy of PIN and the corresponding PC was significantly associated. In four cases, PIN was DNA aneuploid while the associated PC was DNA diploid. These results support the hypothesis that high-grade PIN is a neoplastic precursor of prostatic adenocarcinoma and suggest that further karyotypic instability may result in invasive adenocarcinoma with different DNA content detectable by image analysis.