Correlation of phospholipid metabolites with prostate cancer pathologic grade, proliferative status and surgical stage - impact of tissue environment

Abstract

This study investigates the relationship between phospholipid metabolite concentrations, Gleason score, rate of cellular proliferation and surgical stage in malignant prostatectomy samples by performing one- and two-dimensional, high-resolution magic angle spinning, total correlation spectroscopy, pathology and Ki-67 staining on the same surgical samples. At radical prostatectomy, surgical samples were obtained from 49 patients [41 with localized TNM stage T1 and T2, and eight with local cancer spread (TNM stage T3)]. Thirteen of the tissue samples were high-grade prostate cancer [Gleason score: 4 + 3 (n = 7); 4 + 4 (n = 6)], 22 low-grade prostate cancer [Gleason score: 3 + 3 (n = 17); 3 + 4 (n = 5)] and 14 benign prostate tissues. This study demonstrates that high-grade prostate cancer shows significantly higher Ki-67 staining and concentrations of phosphocholine (PC) and glycerophosphocholine (GPC) than does low-grade prostate cancer (2.4 ± 2.8% versus 7.6 ± 3.5%, p < 0.005, and 0.671 ± 0.461 versus 1.87 ± 2.15 mmolal, p < 0.005, respectively). In patients with local cancer spread, increases in [PC + GPC + PE + GPE] (PE, phosphoethanolamine; GPE, glycerophosphoethanolamine] and Ki-67 index approached significance (4.2 ± 2.5 versus 2.7 ± 2.4 mmolal, p = 0.07, and 5.3 ± 3.8% versus 2.9 ± 3.8%, p = 0.07, respectively). PC and Ki-67 were significantly lower and GPC higher in prostate tissues when compared with cell cultures, presumably because of a lack of important stromal-epithelial interactions in cell cultures. The findings of this study will need to be validated in a larger cohort of surgical patients with clinical outcome data, but support the role of in vivo (1)H MRSI in discriminating between low- and high-grade prostate cancer based on the magnitude of elevation of the in vivo total choline resonance.