Table 4.
Primary tumors differentiated based on combined immunostaining of the marker for proliferation Ki67 and prostate specific antigen (PSA), in relation to clinical variables, epithelial and stromal markers, and the transcriptomic metastasis subtypes MetA-C.
| Ki67 Low, PSA High a | Ki67 High, PSA Low a | Others a | |
|---|---|---|---|
| n = 26 | n = 34 | n = 38 | |
| Age at diagnosis (yrs.), n = 97 | 71 (65; 78) | 70 (65; 76) | 68 (64; 73) |
| Serum PSA at diagnosis (ng/mL), n = 96 | 110 (41; 940) | 44 (26; 96) | 97 (49; 590) |
| ISUP, n = 98 | 4 (3; 5) | 4 (4; 5) | 4 (3; 4) |
| Primary tumors | |||
| Ki67 epithelium (%), n = 98 | 7.5 (6; 10) | 22 (18; 37) *** | 12 (7.0; 16) * |
| PSA epithelium (score), n = 98 | 12 (9; 12) | 6 (3; 7) *** | 8 (6; 10) *** |
| AR epithelium (score), n = 97 | 12 (8; 12) | 12 (8; 12) | 12 (9; 12) |
| ERG epithelium (pos./total), n = 86 | 5/22 | 11/30 | 16/34 |
| Ki67 stroma (%), n = 95 | 1 (0.5; 1.5) | 2.8 (1.1; 4.0) *** | 1.2 (0.63; 2.0) |
| AR stroma (%), n = 97 | 23 (16; 34) | 9.5 (6.0; 18) *** | 20 (14; 28) |
| SMA stroma density (%), n = 69 | 16 (13; 18) | 15 (11; 18) | 16 (12; 18) |
| SDF-1 stroma density (%), n = 67 | 2.9 (1.6; 4.2) | 3.4 (2.3; 4.1) | 3.1 (1.7; 3.9) |
| PDGFRβ stroma density (%), n = 61 | 6.1 (3.6; 10) | 4.9 (3.8; 7.9) | 9.0 (5.8; 13) |
| ERG endothelium density (%), n = 84 | 1.2 (0.83; 1.5) | 0.83 (0.63; 1.5) | 0.89 (0.66; 1.3) |
| Metastases | |||
| Ki67 epithelium (%), n = 98 | 12 (6.0; 18) | 19 (11; 35) ** | 18 (10; 25) * |
| PSA epithelium (score), n = 98 | 9 (6; 12) | 4 (1; 6) *** | 8 (6; 10) |
| AR epithelium (score), n = 93 | 9 (4; 12) | 8 (3; 12) | 8 (4; 12) |
| ERG epithelium (pos./total), n = 92 | 4/25 | 6/32 | 15/35 * |
| Ki67 stroma (%), n = 78 | 3.5 (2.0; 6.5) | 6.0 (4.0; 8.0) * | 4.0 (2.0; 7.5) |
| AR stroma (%), n = 69 | 2.7 (1.6; 6.0) | 2 (1.3; 4.0) | 3.4 (2.0; 4.0) |
| SMA stroma density (%), n = 72 | 4.7 (3.2; 6.8) | 5.2 (4.2; 8.5) | 5.3 (3.0; 6.3) |
| SDF-1 stroma density (%), n = 76 | 5.4 (4.1; 6.6) | 4.4 (3.0; 5.6) | 4.5 (3.4; 6.3) |
| PDGFRβ stroma density (%), n = 60 | 10 (8.3, 12) | 9.6 (5.4; 13) | 9.0 (6.4; 12) |
| ERG endothelium density (%), n = 82 | 0.87 (0.55; 1.2) | 1.3 (0.95; 2.0) ** | 0.92 (0.80; 1.4) |
| MetA b (%), n = 70 | 78 (62; 86) | 37 (9; 60) *** | 70 (46; 84) |
| MetB b (%), n = 70 | 10 (1; 18) | 31 (5; 65) * | 14 (7; 26) |
| MetC b (%), n = 70 | 11 (0; 26) | 11 (0; 54) | 4 (0; 19) |
Marker values are shown as median (25th and 75th percentiles), * p < 0.05, ** p < 0.01, *** p < 0.001. a A combinatory immunoreactivity score for Ki67 and PSA constructed based on the median values (13% and 8%, respectively) stratified primary tumors into 3 groups: “low Ki67, high PSA”, “high Ki67, low PSA”, and “others”. b Fractions (%) of the metastasis subtypes MetA-C were estimated based on expression levels of 157 MetA-C-associated genes, as previously described [4]. ERG, ETS-related gene; Ki67, marker for proliferation; PSA, prostate specific antigen; AR, androgen receptor; SMA, smooth muscle actin; SDF-1, stroma derived factor 1; PDGFRβ, platelet-derived growth factor receptor β.