The role of Polyamines and Ornithine decarboxylase in sporadic adenomatous polyps of the colon

INTRODUCTION. Polyamines (PA) - Putrescine (PUT), Spermidine (SPD), Spermine (SPM) - and Ornithine decarboxylase (ODC), their rate-limiting enzyme, play a key role in cell proliferation and differentiation. PA and ODC have been investigated in different pre-neoplastic lesions of digestive tract. They are reported to be sensitive biomarkers of potential cancer risk in colonic mucosa, especially when genetic factors occur, i.e. familial adenomatous polyposis. In sporadic adenomatous polyps of the colon the role of PA and ODC is less clear. In patients affected by sporadic polyps of the colon, we have investigated the relation between the histologic type, related to the dysplasia degree, and the mucosal levels of both PA and ODC. MATERIALS AND METHODS. Patients (age: 32-79 yrs), after giving their informed consent, were admitted to the study whenever sporadic polyps were observed during colonoscopy. Ten subjects with suspected colon disease, endoscopically unconfirmed, were used as controls. The removed polyps underwent histological examination under the supervision of a 20 yrs-experienced pathologist. Mucosal biopsy specimens were obtained 2-3 cm distant from the polyp, as well as in the unaffected mucosa of the controls. The specimens were immediately frozen with liquid nitrogen and stored at -80°C up to the determinations. The PA contents of perchloric acid extracts of biopsy specimens were determined by means of high-performance liquid chromatography according to Stefanelli et al. PA values are expressed as nmol/g protein. ODC activity was determined by means of radiometric method. RESULTS AND COMMENTS. The histological examination of removed polyps evidences, according to the current classification, three groups with relation to the type of adenoma and to the degree of dysplasia, i.e.: Tubular with mild dysplasia, Tubulovillous with mild dysplasia, and Tubulovillous with moderate dysplasia. The tissue levels of PA and ODC obtained from the colon mucosa in which the polyps have been found are expressed in the TABLE with relation to the histology. ODC activity increased in the colon mucosa surrounding the removed adenoma, even though the levels were significantly higher than controls only for Tubulovillous type with higher dysplasia degree. The SPD levels were higher than controls in the Tubulovillous type with a slight increase from mild to moderate dysplasia degree. However among PA, SPD was significantly increased versus controls in Tubulovillous adenoma with moderate dysplasia degree. Previous investigations have evidenced SPD increase when cell cylce starts from G1 to mitosis, suggesting the close relation to cell proliferation. Our results showed that in sporadic polyps of the colon with enhanced dysplasia degree both SPD and ODC are significantly increased. This behavior would confirm the important role of such biomarkers on investigating the potential risk of colon cancer.