Change in telomerase activity during human colorectal carcinogenesis.

Telomerase activities in endoscopically resected colorectal adenomas, surgically resected colorectal cancers and adjacent normal colonic mucosa were examined semiquantitatively by a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay. All normal mucosa (n = 15) presented 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 telomerase activity in the adenomas (n = 14) was up-regulated (2.01 +/- 0.22) relative to the normal mucosa. The telomerase activity in the high-grade atypia (severe atypia and carcinoma in situ) (2.58 +/- 0.34) was significantly higher than that in the low-grade (mild and moderate) atypia (1.59 +/- 0.18) (P < 0.05), and the adenomas 10 mm or more in diameter presented significantly higher 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 (> or = 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 normal colonic mucosa is gradually activated during the course of colorectal carcinogenesis.