Significance of abnormal diploid DNA histograms in localized prostate cancer and adjacent benign prostatic tissue

To clarify the relationship of DNA ploidy to tumor grade and volume, 32 clinical Stage B prostate cancers, with low and high Gleason scores and small and large tumor volumes, were compared with adjacent histologically normal prostate tissue and with samples from benign prostatic hyperplasia (BPH). All 22 samples from benign glands were diploid, with 2.7 +/- 1.2% tetraploid (4C) cells. Samples from cancer-bearing glands were considered diploid (normoploid) if they had a major diploid (2C) peak and a small 4C peak with the percentage of cells falling within 3 standard deviations of the figure found for BPH. Abnormal ploidy included abnormal diploid (6.3-14.9% 4C), tetraploid (> or = 15% 4C), and aneuploid samples (peaks not at 2C or 4C). Abnormal DNA ploidy was found to be related to tumor volume. All five tumors smaller than 0.4 cm3 and their adjacent benign tissue were normoploid; however, 10 of 13 cancers with volumes of 0.4-1 cm3 had abnormal ploidy (9 abnormal diploid, 1 tetraploid) and 6 of 9 of the adjacent benign tissue samples also were abnormal diploid. All larger tumors (> 1 cm3) showed abnormal ploidy (7 abnormal diploid, 3 tetraploid, 5 aneuploid). For large tumors, abnormal ploidy was present in 10 of 13 of the adjacent benign areas (8 abnormal diploid, 2 benign areas that were clearly aneuploid). Abnormal diploid cancers are intermediate forms between diploid and tetraploid tumors, as defined above. Although they have fewer 4C cells than tetraploid cancers, they have equivalent numbers of hypertetraploid cells (BPH: 1.3 +/- 0.9%; abnormal diploid: 10.8 +/- 5.4%; tetraploid: 11.1 +/- 6.8% hypertetraploid cells). Thus, the authors propose that abnormal diploid cancers represent an early stage in ploidy progression. DNA ploidy abnormalities also occur in benign prostatic tissue adjacent to many prostate cancers, consistent with the concept that human prostatic cancer is a field-change disease.