Zhao Ronghua, Berho Mariana, Nogueras Juan, Sands Dana, Weiss Eric, Wexner Steven, Giardiello Francis M, Cruz-Correa Marcia
Department of Colorectal Surgery, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331, USA.
Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1819-22. doi: 10.1158/1055-9965.EPI-04-0803.
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.
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.
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).
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.
胰岛素样生长因子-II（IGF-II）刺激细胞增殖，被认为是结直肠癌的一个潜在危险因素。IGF-II的肿瘤水平似乎与结直肠癌细胞增殖呈正相关。本研究调查了结直肠肿瘤患者循环IGF-II与肿瘤及配对正常黏膜增殖细胞指数（PCI）之间的关联。
采用酶联免疫吸附测定法（ELISA）测定外周血浆中循环IGF-II水平（ng/mL）。使用抗Ki-67一抗对肿瘤或配对正常黏膜中的增殖细胞进行免疫组织化学染色。采用计算机图像分析，PCI表示为Ki-67阳性细胞数/总计数细胞数的百分比。
共评估了64例患者；45例患有结直肠肿瘤（男性27例/女性18例；平均年龄66.8±11.8岁），19例患有增生性息肉（男性6例，女性13例；平均年龄58.4±14.4岁）。在结直肠肿瘤患者中，血液IGF-II水平与配对正常黏膜中的PCI呈正相关（r = 0.46，P < 0.05），但与肿瘤中的PCI无相关性。在增生性息肉患者中，血液IGF-II水平与息肉中的PCI无相关性。Dukes' C/D期或淋巴结阳性的结直肠癌患者血液IGF-II水平较高（P < 0.01）。
结直肠肿瘤患者正常结肠黏膜中循环IGF-II与PCI呈正相关，提示IGF-II可能通过刺激细胞增殖在启动致癌途径中发挥作用。晚期结直肠癌患者血液IGF-II升高，表明它可能促进结直肠癌进展，是预后不良的一个有用标志物。
