The Role of High-Resolution Magic Angle Spinning 1H Nuclear Magnetic Resonance Spectroscopy for Predicting the Invasive Component in Patients with Ductal Carcinoma In Situ Diagnosed on Preoperative Biopsy

Abstract

The purpose of this study was to evaluate the role of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy in patients with ductal carcinoma in situ (DCIS) diagnosed on preoperative biopsy. We investigated whether the metabolic profiling of tissue samples using HR-MAS 1H NMR spectroscopy could be used to distinguish between DCIS lesions with or without an invasive component. Our institutional review board approved this combined retrospective and prospective study. Tissue samples were collected from 30 patients with pure DCIS and from 30 with DCIS accompanying invasive carcinoma. All patients were diagnosed with DCIS by preoperative core-needle biopsy and underwent surgical resection. The metabolic profiling of tissue samples was performed by HR-MAS 1H NMR spectroscopy. All observable metabolite signals were identified and quantified in all tissue samples. Metabolite intensity normalized by total spectral intensities was compared according to the tumor type using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). By univariate analysis, the metabolite concentrations of choline-containing compounds obtained with HR-MAS 1H NMR spectroscopy did not differ significantly between the pure DCIS and DCIS accompanying invasive carcinoma groups. However, the GPC/PC ratio was higher in the pure DCIS group than in the DCIS accompanying invasive carcinoma group (p = 0.004, Bonferroni-corrected p = 0.064), as well as the concentration of myo-inositol and succinate. By multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles could clearly discriminate between pure DCIS and DCIS accompanying invasive carcinoma. Our preliminary results suggest that HR-MAS MR metabolomics on breast tissue may be able to distinguish between DCIS lesions with or without an invasive component.

Recent Advances in NMR-Based Metabolomics

“…In another study, HRMAS NMR was used to distinguish between ductal carcinoma in situ (DCIS) lesions with or without an invasive component. 106 It showed that the GPC/PC ratio as well as multivariate models discriminated between pure DCIS and DCIS accompanying invasive carcinoma. HRMAS NMR was also used to investigate breast tumor cell lines MCF-7 and MDA-MB-231, along with the nontumor breast cell line MCF-10A, to evaluate cancer metabolism in intact cells.…”

Proton MR spectroscopy in the breast: Technical innovations and clinical applications

“…However, the glycerophosphocholine/phosphocholine ratio as well as the concentrations of myo‐inositol and succinate was significantly higher in the pure DCIS than in DCIS without an invasive component. Orthogonal projections to latent structure‐discriminant analysis models based on the metabolic profiles were able to clearly discriminate between pure DCIS and DCIS without an invasive component …”

“…Orthogonal projections to latent structure-discriminant analysis models based on the metabolic profiles were able to clearly discriminate between pure DCIS and DCIS without an invasive component. 83 MRS also allows the noninvasive identification and monitoring of triple-negative breast cancer (TNBC) metabolic aberrations. Several human and experimental studies have shown that phosphatidylcholine metabolism is altered in TNBCs and phosphocholine levels are increased in TNBCs.…”

Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by 1H HR-MAS NMR Metabolomics

“…Attesting to clinical translatability, 1 H HR-MAS, thanks to its execution rapidity and capacity to preserve samples for further analyses, has already shown promising results in other cancers. For example, it has been successfully adopted to determine sample quality in real-time during surgery [32], or to aid diagnosis in tumor biopsies [12,33,34]. In the field of bone cancer, further studies may extend 1 H HR-MAS analyses to larger patient cohorts to characterize and compare pathologic conditions.…”