Differentiation of human tumors from nonmalignant tissue by natural‐abundance 13C NMR spectroscopy

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Abstract
High‐quality, high‐resolution, proton‐decoupled natural‐abundance 13C NMR spectra have been obtained in vitro at 100.6 MHz from unprocessed human pathology specimens of tumors and adjacent nonneoplastic control tissues from lung, colon, and prostate. In these preliminary studies, specific molecular parameters were identified from the spectra that distinguished neoplastic from nonneoplastic tissue of a given organ in all sites studied. The NMR results were congruent with data derived from histochemical and biochemical examinations of the tissues and with previous studies using non‐NMR methods. In particular, a comparison of the spectra of prostatic adenocarcinoma with that of adjacent hyperplastic tissue revealed the following differences: The tumors contained (1) larger amounts of triacylglycerols, (2) smaller amounts of citrate, and (3) acidic mucins. These transformation‐associated deviations from the normally high amounts of citrate and low amounts of lipids in the prostate are consistent with an alteration in either the concentration or the activity of ATP‐citrate lyase in the tumors. The 13C NMR spectra of colonic adenocarcinoma tissue showed that this tumor type contained (1) smaller signals from triacylglycerols, (2) larger signals from phospholipids and lactate, and (3) decreased lipid fatty acyl chain saturation, when compared to spectra from adjacent normal colon. Colloid carcinoma, another variant of colonic carcinoma, showed prominent 13C resonances from glycoproteins, which were absent from the spectra of normal colon, and from spectra from the more common pattern of colonic adenocarcinoma. Smaller 13C NMR signals from mucins and other proteins, and the presence of triacylglycerol signals distinguished poorly differentiated lung carcinoma and from nonmalignant lung tissue. These results indicate that natural‐abundance 13C NMR spectroscopy may constitute a unique, nondestructive method, for the simultaneous measurement of a large number of tissue metabolites and structural components of significance to the study and diagnosis of a wide range of human tumors. © 1988 Academic Press, Inc.