Intratumoral Agreement of High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopic Profiles in the Metabolic Characterization of Breast Cancer

Abstract

High-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy data may serve as a biomarker for breast cancer, with only a small volume of tissue sample required for assessment. However, previous studies utilized only a single tissue sample from each patient. The aim of this study was to investigate whether intratumoral location and biospecimen type affected the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopyThis prospective study was approved by the institutional review board and informed consent was obtained. Preoperative core-needle biopsies (CNBs), central, and peripheral surgical tumor specimens were prospectively collected under ultrasound (US) guidance in 31 patients with invasive breast cancer. Specimens were assessed with HR-MAS MR spectroscopy. The reliability of metabolite concentrations was evaluated and multivariate analysis was performed according to intratumoral location and biospecimen type.There was a moderate or higher agreement between the relative concentrations of 94.3% (33 of 35) of metabolites in the center and periphery, 80.0% (28 of 35) of metabolites in the CNB and central surgical specimens, and 82.9% (29 of 35) of metabolites between all 3 specimen types. However, there was no significant agreement between the concentrations of phosphocholine (PC) and phosphoethanolamine (PE) in the center and periphery. The concentrations of several metabolites (adipate, arginine, fumarate, glutamate, PC, and PE) had no significant agreement between the CNB and central surgical specimens.In conclusion, most HR-MAS MR spectroscopic data do not differ based on intratumoral location or biospecimen type. However, some metabolites may be affected by specimen-related variables, and caution is recommended in decision-making based solely on metabolite concentrations, particularly PC and PE. Further validation through future studies is needed for the clinical implementation of these biomarkers based on data from a single tissue sample.

Impact of intratumoral heterogeneity of breast cancer tissue on quantitative metabolomics using high‐resolution magic angle spinning 1H NMR spectroscopy

“…Interestingly, all cores but one were correctly classified (Figure A), suggesting that cores sampled from the same tumor were, in general, more similar than cores sampled from two different tumors, despite the observed intratumoral variability. This is in agreement with the conclusion of Park et al, where the authors compared metabolite levels in the center of the tumor with those observed at the tumor periphery in surgically resected breast cancer tissue. Overall, the authors concluded that the intratumoral location had a limited influence on the observed metabolite levels .…”

“…This is in agreement with the conclusion of Park et al, where the authors compared metabolite levels in the center of the tumor with those observed at the tumor periphery in surgically resected breast cancer tissue. Overall, the authors concluded that the intratumoral location had a limited influence on the observed metabolite levels . The results of the present investigation also agree with the findings mentioned by Cao et al, who sampled multiple biopsies and suggested that the interpatient variation was higher than the intrapatient variation.…”

“…Of these, to our knowledge, two had not been reported previously in primary breast cancer tissue using this technique, namely 3‐hydroxybutyrate and glutathione. However, only a small number of previous studies have specified metabolite concentrations in μmol/g in primary breast cancer or xenograft tissue and, in these studies, concentrations were often presented for only a smaller subset of the metabolites reported in the current study. The concentrations reported here for phosphocholine, glycerophosphocholine, glycine, taurine, creatine, myo‐inositol, succinate and lactate were in a similar range to those described previously for primary tumor tissue of human breast cancer (Supporting Information File S10).…”

“…Moreover, long‐term storage at –80°C and repeated freezing and thawing of the tissue have also been investigated. However, only one previous study has comprehensively addressed the impact of intratumoral variability on the metabolic profile of breast cancer tissue. When analyzing intact tumor tissue, an important question is whether a single biopsy, or one smaller sample of a larger, surgically resected tumor specimen, is representative of the entire tumor.…”

Applications of high‐resolution magic angle spinning MRS in biomedical studies II—Human diseases

“…Studies of breast cancer (BrCa) have shown HRMAS MRS to be a promising tool in cancer diagnosis, treatment monitoring, and prediction of prognosis. [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73] Here, we will focus our review on four interesting aspects: metabolic differences between malignant and non-malignant breast tissues, correlations between metabolites and pathologic features of BrCa, predictions of the response to the clinical treatment and the prognosis of BrCa with metabolic information, and the relationships of metabolite, gene, and protein information.…”