Sitter Beathe, Lundgren Steinar, Bathen Tone F, Halgunset Jostein, Fjosne Hans E, Gribbestad Ingrid S
Department of Circulation and Medical Imaging, Norwegian University of Technology and Science, 7491 Trondheim, Norway.
NMR Biomed. 2006 Feb;19(1):30-40. doi: 10.1002/nbm.992.
Breast cancer is the most frequent form of cancer in women and improved diagnostic methods are desirable. Malignant cells have altered metabolism and metabolic mapping might become a tool in cancer diagnostics. High-resolution magic angle spinning (HR MAS) MR spectroscopy of tissue biopsies provides detailed information on metabolic composition. The 600 MHz 1H HR MAS spectra were acquired of breast cancer tissue from 85 patients and adjacent non-involved tissue from 18 of these patients. Tissue specimens were investigated by microscopy after MR analysis. The resulting spectra were examined by three different approaches. Relative intensities of glycerophosphocholine (GPC), phosphocholine (PC) and choline were compared for cancerous and non-involved specimens. Eight metabolites, choline, creatine, beta-glucose, GPC, glycine, myo-inositol, PC and taurine, were quantified from the recorded spectra and compared with tumor histological type and size, patient's lymph node status and tissue composition of sample. The spectra were also compared with tumor histological type and size, lymph node status and tissue composition of samples using principal component analysis (PCA). Tumor samples could be distinguished from non-involved samples (82% sensitivity, 100% specificity) based on relative intensities of signals from GPC, PC and choline in 1H HR MAS spectra. Tissue concentrations of metabolites showed few differences between groups of samples, which can be caused by limitations in the quantification procedure. Choline and glycine concentrations were found to be significantly higher in tumors larger than 2 cm compared with smaller tumors. PCA of MAS spectra from patients with invasive ductal carcinomas indicated a possible prediction of spread to axillary lymph nodes. Metabolite estimates and PCA of MAS spectra were influenced by the percentage of tumor cells in the investigated specimens.
乳腺癌是女性中最常见的癌症形式，因此需要改进诊断方法。恶性细胞具有改变的代谢，代谢图谱可能成为癌症诊断的一种工具。组织活检的高分辨率魔角旋转（HR MAS）磁共振波谱提供了有关代谢成分的详细信息。采集了85例患者乳腺癌组织以及其中18例患者的相邻未受累组织的600 MHz 1H HR MAS波谱。在磁共振分析后，通过显微镜检查组织标本。所得波谱采用三种不同方法进行检查。比较了癌组织和未受累标本中甘油磷酸胆碱（GPC）、磷酸胆碱（PC）和胆碱的相对强度。从记录的波谱中对胆碱、肌酸、β-葡萄糖、GPC、甘氨酸、肌醇、PC和牛磺酸这八种代谢物进行定量，并与肿瘤组织学类型和大小、患者淋巴结状态以及样本的组织成分进行比较。还使用主成分分析（PCA）将波谱与肿瘤组织学类型和大小、淋巴结状态以及样本的组织成分进行比较。基于1H HR MAS波谱中GPC、PC和胆碱信号的相对强度，肿瘤样本可与未受累样本区分开来（敏感性82%，特异性100%）。代谢物的组织浓度在样本组之间差异不大，这可能是由定量程序的局限性导致的。发现肿瘤大于2 cm的患者中胆碱和甘氨酸浓度显著高于较小肿瘤的患者。浸润性导管癌患者MAS波谱的PCA表明可能预测腋窝淋巴结转移。代谢物估计值和MAS波谱的PCA受所研究标本中肿瘤细胞百分比的影响。
