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.

Eun Young Chae,Ye Eun Shim,Jeong Hyun Lee,Hee Jin Lee,Gyungyub Gong,Ji Hoon Shin,Woo Jung Choi,Hee Jung Shin,Siwon Kim,Hyeon-Man Baek,Joo Hee Cha,Suhkmann Kim,Hak Hee Kim,Dahye Yoon,Peter Lundberg

doi:10.1371/journal.pone.0161038

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.

Highlights

The diagnosis of ductal carcinoma in situ (DCIS) is more common with the more widespread use of mammographic screening [1], there is substantially imperfect understanding of the biology and clinical outcome of DCIS [2]
The purpose of our current study was to evaluate the role of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy in patients with DCIS diagnosed on preoperative biopsy
We investigated whether the metabolic profiling of tissue samples using HR-MAS 1H NMR spectroscopy would help to distinguish between DCIS lesions with or without an invasive component

Summary

Introduction

The diagnosis of ductal carcinoma in situ (DCIS) is more common with the more widespread use of mammographic screening [1], there is substantially imperfect understanding of the biology and clinical outcome of DCIS [2]. HR-MAS analysis of tissue samples provides peaks representative of metabolites [5] This method provides comprehensive and detailed information on the biochemical composition of the tissue and can be used in non-targeted analysis to identify surrogate markers predicting malignant transformation or treatment response. HR-MAS MR spectroscopy has been used in breast cancer studies, for metabolite identification, diagnosis, characterization, and correlation with prognostic markers of breast cancer and treatment response monitoring [5,6,7,8]. These studies mainly focused on the analysis of invasive breast cancer and little is known regarding the use of HR-MAS to evaluate DCIS of the breast

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