N-acetyl resonances in in vivo and in vitro NMR spectroscopy of cystic ovarian tumors.
An unassigned and prominent resonance in the region from delta 2.0-2.1 ppm has frequently been found in the in vivo MR spectra of cancer patients. We demonstrated the presence of this resonance with in vivo MRS in the cyst fluid of a patient with an ovarian tumor. (1)H-NMRS on the aspirated cyst fluid of this patient confirmed the observation. A complex of resonances was observed between 2.0 and 2.1 ppm. It was also present in 11 additional ovarian cyst fluid samples randomly chosen from our biobank. The resonance complex was significantly more prominent in samples from mucinous tumors than in samples from other histological subtypes. A macromolecule (>10 kDa) was found responsible for this complex of resonances. A correlation spectroscopy (COSY) experiment revealed cross peaks of two different types of bound sialic acid suggesting that N-glycans from glycoproteins and/or glycolipids cause this resonance complex. In the literature, plasma alpha-1 acid glycoprotein (AGP), known for its high content of N-linked glycans, has been suggested to contribute to the delta 2.0-2.1 spectral region. The AGP cyst fluid concentration did not correlate significantly with the peak height of the delta 2.0-2.1 resonance complex in our study. AGP may be partly responsible for the resonance complex but other N-acetylated glycoproteins and/or glycolipids also contribute. After deproteinization of the cyst fluid, N-acetyl-L-aspartic acid (NAA) was found to contribute significantly to the signal in this spectral region in three of the 12 samples. GC-MS independently confirmed the presence of NAA in high concentration in the three samples, which all derived from benign serous tumors. We conclude that both NAA and N-acetyl groups from glycoproteins and/or glycolipids may contribute to the delta 2.0-2.1 ppm resonance complex in ovarian cyst fluid. This spectral region seems to contain resonances from biomarkers that provide relevant clinical information on the type of ovarian tumor.
Kolwijck
Eva
E
Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. E.Kolwijck@obgyn.umcn.nl
Engelke
Udo F
UF
van der Graaf
Marinette
M
Heerschap
Arend
A
Blom
Henk J
HJ
Hadfoune
M'Hamed
M
Buurman
Wim A
WA
Massuger
Leon F
LF
Wevers
Ron A
RA
D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D020420:Cyst Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010048:Ovarian Cysts / Q000737:chemistry / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology; D055815:Young Adult
D001224:Aspartic Acid; C000179:N-acetylaspartate