Positive correlation of insulin-like growth factor-II with proliferating cell index in patients with colorectal neoplasia.
BACKGROUND
Insulin-like growth factor-II (IGF-II) stimulates cell proliferation and is considered a potential risk factor for colorectal cancer. Tumor levels of IGF-II seem to positively correlate with colorectal cancer cell proliferation. This investigation examined the association of circulating IGF-II to the proliferating cell index (PCI) of tumor and matched normal mucosa in patients with colorectal neoplasia.


METHODS
Circulating IGF-II level (ng/mL) was determined in the peripheral blood plasma by ELISA. The proliferating cells in tumor or matched normal mucosa were immunohistochemically stained using the primary antibody against Ki-67. Computer image analysis was used and PCI was expressed as the percentage of Ki-67-positive cells/total counted cells.


RESULTS
Sixty-four patients were evaluated; 45 had colorectal neoplasia (27 males/18 females; mean age, 66.8 +/- 11.8 years) and 19 had hyperplastic polyps (6 males and 13 females; mean age, 58.4 +/- 14.4 years). Among patients with colorectal neoplasia, blood IGF-II levels were positively correlated with PCI in the matched normal mucosa (r = 0.46, P < 0.05) but not in the tumor. In patients with hyperplastic polyps, blood IGF-II levels were not correlated with the PCI in the polyps. Blood IGF-II levels were higher in colorectal cancer patients with Dukes' C/D stage (P < 0.01) or with positive lymph nodes (P < 0.01).


CONCLUSIONS
Circulating IGF-II positively correlated with PCI in normal colonic mucosa of patients with colorectal neoplasia, suggesting that IGF-II may have a role in initiating the carcinogenic pathway by stimulating cell proliferation. Blood IGF-II was increased in advanced colorectal cancer, indicating that it might enhance colorectal cancer progression and be a useful marker of poor prognosis.
Zhao
Ronghua
R
Department of Colorectal Surgery, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331, USA.
Berho
Mariana
M
Nogueras
Juan
J
Sands
Dana
D
Weiss
Eric
E
Wexner
Steven
S
Giardiello
Francis M
FM
Cruz-Correa
Marcia
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; C035170:IGF2 protein, human; D011506:Proteins; D007335:Insulin-Like Growth Factor II