IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer.
Insulin-like growth factors (IGF-1 and IGF-2) and the IGF-1 membrane receptor (IGF-1R) have been found to play a critical role in the carcinogenesis of several tumors, among them colorectal cancer (CRC). To study the prognostic impact of these molecules, a total number of 713 cases of CRC were examined for the expression of IGF-1, IGF-2, and IGF-1R. The results were correlated with other clinicopathological data and clinical follow-up. IGF-1 expression was noted in 53 (7.5%), IGF-2 in 88 (12.6%), and IGF-1R in 698 (99.6%) of the cases. There were significant associations between the two growth factors ( P<0.00001), between IGF-1 and Ki-67 proliferation activity ( P<0.05), and between IGF-2 and tumor stage ( P<0.005). IGF-2 positivity was significantly correlated to a worse clinical outcome ( P<0.005) only in univariate, but not in multivariate, survival analysis. A similar trend was obtained for patients with IGF-1-positive CRC, but reached statistical significance only in limited tumor stages (pT1/pT2; P<0.01). Although the synchronous expression of IGF-1, IGF-2, and IGF-1R in a subset of CRC is consistent with an auto-/paracrine loop of cancer cell autostimulation, the prognostic effect of IGF-1 and IGF-2 expression seems to be of limited value. However, the identification of IGF-positive CRC might be beneficial for predictive reasons, as new molecular therapeutic approaches are aimed at the IGF system and related pathways.
Peters
Gerrit
G
Hannover Medical School, Department of Pathology, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Gongoll
Silvia
S
Langner
Cord
C
Mengel
Michael
M
Piso
Pompiliu
P
Klempnauer
Jürgen
J
Rüschoff
Josef
J
Kreipe
Hans
H
von Wasielewski
Reinhard
R
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D016019:Survival Analysis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C065700:myotrophin; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1