DETECTION OF TELOMERASE ACTIVITY IN EXFOLIATED CANCER-CELLS IN COLONIC LUMINAL WASHINGS AND ITS RELATED CLINICAL IMPLICATIONS

Telomerase is a ribonucleoprotein capable of replacing telomeric DNA s equences that are lost at each cell division. Under normal circumstanc es, it is active in rapidly dividing embryonic cells and in stem cell populations but not in terminally differentiated somatic cells. Much a ttention has recently focused on the hypothesis that activity of this enzyme is necessary for cells to become immortal. This predicts that t elomerase activity should be detectable in malignant cells and tissues but not in their normal counterparts, which slowly senesce and die. i n accordance with this notion, telomerase activity has been reported i n a wide range of malignancies, including those of the gastrointestina l tract, breast and lung. In the present study, we used a polymerase c hain reaction (PCR)-based assay for telomerase activity, designated th e 'telomeric repeat amplification protocol (TRAP)', to examine initial ly 35 colonic carcinomas, their corresponding normal tissues and 12 in flammatory bowel disease (IBD) lesions. We detected strong enzyme acti vity in 32 (92%) of the 35 colon carcinomas while there was no activit y in 30 (86%) of 35 matched normal colonic tissue specimens and only V ery weak activity in the remainder. Four of seven specimens of ulcerat ive colitis and two of five Crohn's disease lesions were negative, and the rest were only weakly positive. These results led us to examine w hether telomerase could be detected in carcinoma cells exfoliated into the colonic lumen. We assayed lysates of exfoliated cells in luminal washings from colectomy specimens of 15 patients with colon carcinoma and nine with IBD. Telomerase activity was detected in washings from 9 (60%) of the 15 colon carcinoma cases but not in any from cases with IBD, suggesting that it can be a goad marker for the detection of colo n carcinoma, possibly even in non-invasively obtained samples.