Polyamine levels of human colorectal adenocarcinomas are correlated with tumor stage and grade

Background and aims: Cellular proliferation and differentiation are regulated by polyamines and their rate-limiting enzyme ornithine decarboxylase (ODC), both of which are correlated with tumor growth, but their role in differentiation is less clear. We investigated the correlation of ODC activity and polyamine levels with tumor stage and grade with respect to sample recruitment. Patients and methods: We determined ODC activity ([C-14]CO2 release), polyamines (HPLC), and histological staging and grading (TNM classification) of tissue samples from 64 patients with colorectal adenocarcinomas. Results: We found the concentrations of putrescine, spermidine, and NI-acetyl-spermidine and the ODC activity in tumor tissue to be twice as high as in adjacent normal mucosa. A critical parameter affecting ODC activity was ischemic time, which significantly reduced ODC activity levels in tumors (threefold) and in the surrounding normal tissue (ninefold) when the ischemic period exceeded 1 h. By contrast, polyamine content was not affected by ischemia. Total polyamine and spermine concentrations were higher in T3 and T4 than in T2 tumors, but putrescine was higher in T4 than in T3 and T2 tumors. There were significantly higher levels of total polyamines and spermine in moderately differentiated (G2) than in poorly differentiated (G3) tumors. Conclusion: The lower spermidine/spermine ratio in G2 (0.44) compared with that in G3 (0.64) tumors suggests the involvement of the polyamines in colonic cell differentiation. Polyamine content is thus correlated with the tumor stage.