Heterogeneity of prostate cancer in radical prostatectomy specimens

To understand the morphologic and spatial relationships of the various grades of prostate cancer, we investigated whether poorly differentiated cancer usually arises within the center of a large, well-differentiated tumor or more often forms the periphery or leading edge of the tumor.

In a series of one hundred and one completely sectioned whole-mount radical prostatectomy specimens removed from patients with clinical Stage T2 prostate cancer, we mapped the distribution of each of the five Gleason grades and assessed their frequency, proportion, and spatial distribution.

The average number of different grades present in our patients was 2.7 (range 1-5). Over 50 percent of the prostates contained at least three different grades of cancer. The number of different Gleason grades present increased significantly with increasing tumor volume (p < 0.0001). Only 10 percent of the index cancers (largest tumor present) were composed of a single grade and these cancers were small (0.02-1.7 cm3). Among cancers with multiple grades, the most common finding (53%) was a high-grade cancer present within the core of a larger, more well-differentiated tumor; however, the opposite pattern, low-grade cancer present within a larger poorly differentiated cancer, was also common (30%) and predominated in very large cancers (> 10 cm3).

Small prostate cancers are often composed of a single grade, usually Gleason grade 2 or 3. But most palpable cancers contain multiple grades which are arranged in heterogeneous and unpredictable geographic interrelationships.