Gigek Carolina Oliveira, Leal Mariana Ferreira, Lisboa Luara Carolina Frias, Silva Patricia Natalia Oliveira, Chen Elizabeth Suchi, Lima Eleonidas Moura, Calcagno Danielle Queiroz, Assumpção Paulo Pimentel, Burbano Rommel Rodriguez, Smith Marilia de Arruda Cardoso
Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, SP, Brazil.
Growth Horm IGF Res. 2010 Jun;20(3):234-8. doi: 10.1016/j.ghir.2010.02.005. Epub 2010 Mar 9.
The aim of this study was to evaluate IGFBP-3 protein expression, its correlation with gene promoter methylation pattern in gastric carcinogenesis and with clinicopathological characteristics.
Forty-three normal gastric mucosa and 94 adenocarcinoma samples were investigated through methylation specific PCR, after bisulfite modification. Immunohistochemistry was analyzed using peroxidase in 54 gastric cancer and 20 normal gastric mucosa samples.
IGFBP-3 expression was higher in tumor samples than in normal mucosa (p<0.0001). Intestinal type presented a higher frequency of protein expression than diffuse type (p=0.0412). Methylation frequency of IGFBP-3 promoter in gastric samples revealed, respectively, 95.7% and 97.7% in neoplastic and non-neoplastic samples. The frequency of IGFBP-3 methylation did not differ between tumor and normal samples (95.7% versus 97.7%, p=0.7810). We did not observe a significant correlation between IGFBP-3 promoter methylation and protein expression.
In summary, our study did not observe any influence of IGFBP-3 promoter methylation on protein expression. Moreover we propose that IGFBP-3 immunostaining in gastric tissue may be a useful marker for malignancy.
本研究旨在评估胰岛素样生长因子结合蛋白-3(IGFBP-3)蛋白表达,及其在胃癌发生过程中与基因启动子甲基化模式以及临床病理特征的相关性。
对43例正常胃黏膜和94例腺癌样本进行亚硫酸氢盐修饰后,通过甲基化特异性PCR进行研究。对54例胃癌样本和20例正常胃黏膜样本使用过氧化物酶进行免疫组织化学分析。
肿瘤样本中IGFBP-3表达高于正常黏膜(p<0.0001)。肠型的蛋白表达频率高于弥漫型(p=0.0412)。胃样本中IGFBP-3启动子的甲基化频率在肿瘤样本和非肿瘤样本中分别为95.7%和97.7%。肿瘤样本和正常样本之间的IGFBP-3甲基化频率无差异(95.7%对97.7%,p=0.7810)。我们未观察到IGFBP-3启动子甲基化与蛋白表达之间存在显著相关性。
总之,我们的研究未观察到IGFBP-3启动子甲基化对蛋白表达有任何影响。此外,我们提出胃组织中的IGFBP-3免疫染色可能是恶性肿瘤的一个有用标志物。