Distribution of angiogenin and its gene message in colorectal cancer patients and their clinical relevance.
BACKGROUND
[corrected] The distribution of angiogenin (ANG) in normal colorectal and colorectal cancer tissues has not been precisely elucidated, while studies on the clinical significance of ANG have been scanty at best.


METHODS
We investigated the distribution of ANG and its gene message in 58 colorectal cancer and 58 corresponding normal colorectal tissue pairs by immunohistochemistry and in situ hybridization, the circulating ANG levels in sera by ELISA from 94 colorectal cancer patients and 52 healthy volunteers, as well as the clinical significance of ANG expression.


RESULTS
Strong, moderate and weak ANG immunoreactivity of cancer cells was observed in 22, 31 and 5 patients, respectively. ANG immunoreactivity was also observed in interstitial cells in the vicinity of and at the invasion front of cancer cells, as well as in normal superficial epithelial cells and in some interstitial cells. The distribution of the ANG gene message was coherent with the ANG protein localization. The mean serum ANG concentration was significantly (p =0.00005) higher in cancer patients as compared with that in the healthy volunteers and the degree of its elevation was more significant in the more progressed cancer subgroups. The degrees of ANG protein and mRNA expression correlated with serum ANG concentration (p<0.05). Survival analyses revealed a significant correlation between higher serum ANG concentrations (> or = 400ng/ml) and worse disease-free (p=0.003) or disease-specific (p=0.03) survivals.


CONCLUSIONS
These results suggest that ANG is expressed in colorectal cancer cells and in normal colorectal superficial cells as well as in interstitial cells and that serum levels of ANG reflect the degree of tissue ANG expression that could be a predictor of postoperative outcome.
Shimoyama
Shouji
S
Department of Gastrointestinal Surgery, University of Tokyo, Japan. shimoyama-dis@h.u-tokyo.ac.jp
Shimizu
Nobuyuki
N
Tsuji
Eiichi
E
Yamasaki
Kazuki
K
Kawahara
Masaki
M
Kaminishi
Michio
M
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C046366:angiogenin; D012259:Ribonuclease, Pancreatic