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Investigation of metabolite changes in the transition from pre‐invasive to invasive cervical cancer measured using 1 H and 31 P magic angle spinning MRS of intact tissue
Author(s) -
De Silva Sonali S.,
Payne Geoffrey S.,
Thomas Valerie,
Carter Paul G.,
Ind Thomas E. J.,
deSouza Nandita M.
Publication year - 2009
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1302
Subject(s) - metabolite , chemistry , nuclear magnetic resonance , radiochemistry , physics , biochemistry
Abstract The aim of this study was to determine the metabolic changes in the transition from pre‐invasive to invasive cervical cancer using high‐resolution magic angle spinning (HR‐MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). 1 H HR‐MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr–Purcell–Meiboom–Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). 31 P HR‐MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a 1 H‐decoupled pulse‐acquire sequence ( TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with cancer than from patients with high‐grade dyskaryosis, but no differences between non‐cancer groups. Division by histology of the sample also showed increases in choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high‐grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and creatine (P = 0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non‐cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non‐cancer patients (P = 0.0001). Estimated concentrations of choline‐containing metabolites increased from pre‐invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright © 2008 John Wiley & Sons, Ltd.