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

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.

Fourier Transform Infrared Imaging of focal lesions in human osteoarthritic cartilage.

Fourier Transform Infrared Imaging (FTIRI) is a new method for quantitatively assessing the spatial-chemical composition of complex materials. This technique has been applied to examine the feasibility of measuring changes in the composition and distribution of collagen and proteoglycan macromolecules in human osteoarthritic cartilage. Human cartilage was acquired post-operatively from total joint replacement patients. Samples were taken at the site of a focal lesion, adjacent to the lesion, and from relatively healthy cartilage away from the lesion. Sections were prepared for FTIRI and histochemical grading. FTIRI spectral images were acquired for the superficial, intermediate, and deep layers for each sample. Euclidean distance mapping and quantitative partial least squares analysis (PLS) were performed using reference spectra for type-II collagen and chondroitin 6-sulphate (CS6). FTIRI results were correlated to the histology-based Mankin scoring system. PLS analysis found relatively low relative concentrations of collagen (38 +/- 10%) and proteoglycan (22 +/- 9%) in osteoarthritic cartilage. Focal lesions were generally found to contain less CS6 compared to cartilage tissue adjacent to the lesion. Loss of proteoglycan content was well correlated to histological Mankin scores (r=0.69, p<0.0008). The evaluation of biological tissues with FTIRI can provide unique quantitative information on how disease can affect biochemical distribution and composition. This study has demonstrated that FTIRI is useful in quantitatively assessing pathology-related changes in the composition and distribution of primary macromolecular components of human osteoarthritic cartilage.