Enzyme Activity and Protein Patterns as Premalignant Markers in Mucosal Biopsy Specimens from the Large Intestine

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Abstract
Total enzyme activity of glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LD) was measured in homogenates of resected biopsy specimens and in endoscopic biopsy specimens. LD isoenzyme patterns were scanned by a laser technique after agarose gel electrophoresis. Examinations were performed in homogenates of premalignant lesions such as ulcerative colitis and adenomas of the colon, with normal mucosa and carcinomas as control material. Two-dimensional electrophoretic protein patterns were compared for normal mucosa, adenomas, and carcinomas of the large intestine. The mean activity of both G6PD and LD was highest in the presence of dysplasia; only G6PD activity seemed independent of inflammatory changes. The percentage of LD isoenzyme M monomers was significantly higher in homogenates of specimens with dysplastic changes than in specimens with only inflammatory changes. A positive correlation was found between total LD isoenzyme M monomers and LD 5 monomers for the whole material and for each of the histological subgroups of ulcerative colitis. A positive correlation between total LD activity and the percentage of LD 5 monomers was seen only for dysplastic adenomatous, and malignant tissue. The several hundred protein spots seen on 2-dimensional protein maps showed that most of the spots were common for normal mucosa, adenomas, and carcinomas, but differences were also seen. Polyps and carcinomas had strikingly similar protein patterns, different from that of normal mucosa. The rsults of the 2-dimensional protein electrophoresis lend further support to the hypothesis that polyps are precursors of carcinomas of the large intestine. The results of enzyme measurements in specimens from ulcerative colitis support the use of dysplasia as a marker or premalignancy and may suggest a role for measurements of enzyme activity in the elevation of patients with ulcerative colitis. Preliminary examinations of G6PD activity with the high-sensitivity bioluminescence technique for small endoscopic biopsy specimens are reported.

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