Change in telomerase activity during human colorectal carcinogenesis

Telomerase activities in endoscopically resected colorectal adenomas, surgi cally resected colorectal cancels and adjacent normal colonic mucosa were e xamined semiquantitatively by a polymerase chain reaction-based telomeric r epeat amplification protocol (TRAP) assay. All normal mucosa (n=15) present ed weak telomerase activity (mean +/- SE:0.99 +/- 0.00). When the value of 1.00 was arbitrary given to the mean activity of normal mucosa, the telomer ase activity in the adenomas (n=14) was up-regulated (2.01 +/- 0.22) relati ve to the normal mucosa. The telomerase activity in the high-grade atypia ( severe atypia and carcinoma in situ) (2.58 +/- 0.34) was significantly high er than that in the low-grade (mild and moderate) atypia (1.59 +/- 0.18) (P <0.05), and the adenomas 10mm or more in diameter presented significantly h igher telomerase activity (2.56 +/- 0.09) than compared to the smaller ones (1.44 +/- 0.17) (p<0.05). Carcinomas (n=20), showed a telomerase activity that varied from 0.97 to 16.93, which was than the greater mean telomerase activity (6.96 +/- 1.25) noted in the adenomas. The telomerase activity in the carcinomas tended to be higher in the larger (greater than or equal to 4 cm), histologically less-differentiated (moderately differentiated), late -stage (Dukes C+D), and nodal metastatic tumors, suggestive of unfavorable prognosis. These results suggests that the weak telomerase activity in norm al colonic mucosa is gradually activated during the course of colorectal ca rcinogenesis.