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.
Yoshida
R
R
Department of Pathology II, Kansai Medical University, Osaka, Japan.
Kiyozuka
Y
Y
Ichiyoshi
H
H
Senzaki
H
H
Takada
H
H
Hioki
K
K
Tsubura
A
A
D000236:Adenoma / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D003106:Colon; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D003111:Colonic Polyps / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000601:surgery
D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen