Telomerase Activity of Normal Mucosa, Adenomatous Polyp and Cancer of the Colon

ABSTRACT

PURPOSE: Progressive shortening of telomeres, specialized chromosomal structures that have a function in chromosomal protection, positioning and replication, has been linked to cell senescence and aging. Telomeres are usually replicated by telomerase, the activation of which is essential for cells to overcome cellular senescence; and thus, indefinite proliferation/immortality and malignant progression are associated with telomere activity. However, little is known about the telomerase activity in adenomatous polyp and colorectal cancer. METHODS: To determine whether malignant progression depends on the activation of telomerase or not, we analyzed the telomerase activity in the mucosa of normal colon, adenomatous polyp and colorectal cancer by telomeric repeat amplification protocol (TRAP) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: Except for one case in which there was severe inflammation, telomerase activity was not detected in any case of histologically normal colonic mucosa. In contrast, enzyme activity was detected in 58.3% (7/12), 75% (15/20) of adenomatous polyps and colorectal carcinomas, respectively. Of these cases of adernomatous polyps, telomerase activity was positive in 40% (2/5) of tubular type, 66.7% (4/6) of villotubular type and 100% (1/1) of villous type; however, the difference in telomerase activity between tubular and villotubular types was not significant. Of these 20 cases of carcinomas, telomerase activity was positive in 100% (2/2) of well differentiated, 71.4% (10/14) of moderately differentiated and 75% (3/4) of poorly differentiated histologies. Taking into consideration the Dukes' classification, there was no significant difference in telomerase activity among stages A, B and C, except for D. CONCLUSION: These results indicate that telomerase activation in colorectal cancer may well correlate with malignant progression. The detection of telomerase activity may serve as a useful auxiliary tool for the diagnosis of colorectal cancer; nevertheless, the histological type of adenomatouspolyps, the histological differentiation and the stage of cancer may not correlate with telomerase activity.