Masahiro Aihara

Heterogeneity of prostate cancer inradical prostatectomy specimens

OBJECTIVE 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. METHODS 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. RESULTS 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). CONCLUSION 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.

Prostate Specific Antigen and Gleason Grade: An Immunohistochemical Study of Prostate Cancer

Prostate cancer is histologically heterogeneous as reflected in the 5 patterns of the Gleason grading system. Gleason grade correlates with volume, extent and prognosis. Serum prostate specific antigen (PSA) levels also correlate with tumor volume but the degree to which grade correlates with PSA has not been precisely defined. To quantify this relationship further, we prepared maps of each grade of cancer in 86 radical prostatectomy specimens from patients with clinical stage T2 cancer. The median per cent of the volume of cancer per prostate composed of grade 1 was 0%, while it was 1% for grade 2, 84% for grade 3, 5% for grade 4 and 0% for grade 5. We stained 95 cancer foci (grades 1 to 5) in 40 of these specimens for PSA. The presence and intensity (0 to 3+) of staining in more than 33,000 acini (or cells) correlated inversely with grade (p < 0.0001). Nearly all acini in grade 1 and most in grade 2 stained positive (2 to 3+) for PSA; 87% were positive but with less intensity in grade 3. While many grade 4 (79%) and grade 5 (49%) cells were positive, the intensity of staining was weak. Serum PSA levels correlated with total tumor volume (r = 0.67) but serum PSA levels per cm.3 of cancer decreased with increasing grade (r = -0.24 and p < 0.02). These studies confirm the strong inverse correlation between Gleason grade and the PSA content of prostate cancer. Since more than 85% of grade 3 acini stained for PSA and grade 3 made up the largest portion (84%) of cancer, the predominant contributor to serum PSA levels from prostate cancer was Gleason grade 3. The other grades contribute relatively little to the serum PSA levels either because of the small volume (grades 1 and 2) or the diminished PSA content (grades 4 and 5).

Frequency of apoptotic bodies positively correlates with Gleason grade in prostate cancer

Tissue samples from patients with carcinoma of the prostate of various Gleason grades were examined for the frequency of apoptotic bodies. Apoptotic bodies were scored by morphometric methods using hematoxylin-eosin (HE)-stained sections from surgical specimens of prostate cancer. Non-neoplastic prostate tissue adjacent to foci of cancer showed a very low frequency of apoptotic bodies. Significantly larger numbers of apoptotic bodies were observed in the areas of carcinoma than in the non-neoplastic control tissues, regardless of Gleason grade. Interestingly, a positive correlation was noted between apoptotic bodies and increasing Gleason grade. The positive correlation suggests that increased programmed cell death is a feature of the increasing malignant potential that is associated with higher Gleason grade in prostate cancer.

The frequency of apoptosis correlates with the prognosis of Gleason Grade 3 adenocarcinoma of the prostate.

Background. Although localized carcinomas are predominantly moderately differentiated (Gleason Grade 3), they demonstrate markedly different rates of progression. Previously, the authors reported a correlation between apoptosis and the malignant characteristics of carcinoma in the mouse prostate reconstitution model system and between apoptosis and Gleason grade in the human tumor. This study was undertaken to determine whether the frequency of apoptosis correlates with prognosis and to compare the prognostic significance of the apoptotic index with other prognostic features in Gleason Grade 3 carcinomas.