The malignant potential of an individual focus of prostate cancer is difficult to determine. The established pathological features associated with malignant behavior include tumor volume, grade, and invasiveness (local mextension or metastasis).

We used nuclear image analysis to determine the DNA ploidy value of each cancer in a series of 30 radical prostatectomy specimens from patients with early stage prostate cancer in order to further explore the malignant potential of each separate focus of cancer. The volume, grade, invasiveness (extracapsular extension or seminal vesicle invasion), and zone of origin of each of the 63 separate cancers were determined. The DNA ploidy histogram of 200 cancer cells was compared with 50 normal epithelial nuclei on the same Feulgen-stained tissue sections. Sixty % of the cancers were diploid, and 40% were nondiploid. Ploidy correlated with volume and grade. All cancers <0.02 cm3 were diploid; 26% of foci 0.02 to 2.0 cm3 and 82% of foci > 2.0 cm3 were nondiploid. There were 16 cancers of transition zone origin ranging in size from 0.02 to 12.1 cm3 and only one (7.3 cm3) was nondiploid. There were 47 cancers of peripheral zone origin (range, 0.01 to 18.98) and 24 (51%) were nondiploid. Eight of the 24 nondiploid cancers were small (<1.0 cm3), and two were only 0.03 cm3.

We conclude that some very small prostate cancers are nondiploid and that progression of prostate cancer is not a function of volume alone, whereby tumors only acquire full malignant potential at large volumes. Cancers of peripheral zone origin acquire a nondiploid cell population at a smaller volume than do cancers of transition zone origin, further supporting a fundamental difference between cancers arising in these zones.

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Supported in part by the Ralph A. Johnston Foundation through the Ralph A. Johnston Laboratory at Baylor College of Medicine and by Grant CA4719702/03 from the National Cancer Institute, USPHS.

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