Shah N G, Trivedi T I, Tankshali R A, Goswami J A, Shah J S, Jetly D H, Kobawala T P, Patel K C, Shukla S N, Shah P M, Verma R J
Division of Molecular Endocrinology, Gujarat Cancer and Research Institute, Ahmedabad, India.
Int J Biol Markers. 2007 Apr-Jun;22(2):132-43. doi: 10.1177/172460080702200207.
In this study an attempt was made to establish the significance of a battery of molecular alterations and thereby identify risk predictors in oral carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12), hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced stage carcinoma (n=70). Deregulation occurred at an early stage and the number of alterations increased with disease progression. Using multivariate logistic regression analysis, the significant risk predictor for hyperplasia from normal mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16, p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63, p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H-ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key position linking upstream signaling pathways to cell cycle regulation. Gene products of the mitogenic signaling pathway play an equally significant role as cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced-carcinoma sequence and together may provide a reference panel of markers for use in defining premalignant lesions and predicting the risk of malignant transformation and tumor progression.
在本研究中，我们试图确定一系列分子改变的意义，从而识别口腔癌发生过程中的风险预测指标。为此，采用免疫组织化学方法对表皮生长因子受体（EGFR）、信号转导与转录激活因子3（Stat3）、原癌基因H-ras、原癌基因c-myc、抑癌基因p53、细胞周期蛋白D1、抑癌基因p16、视网膜母细胞瘤基因（Rb）、增殖细胞核抗原（Ki-67）和凋亡抑制蛋白Bcl-2在正常黏膜（n=12）、增生（n=35）、发育异常（n=25）、早期癌（n=65）和晚期癌（n=70）中的表达进行定位。失调在早期就已发生，且改变的数量随疾病进展而增加。使用多因素逻辑回归分析，从正常黏膜发展为增生的显著风险预测指标是Ki-67（比值比[OR]=5.75，p=0.021）；从增生发展为发育异常的显著风险预测指标是EGFR（OR=12.96，p=0.002）、Stat3（OR=17.16，p=0.0001）、p16（OR=5.50，p=0.039）和c-myc（OR=5.99，p=0.052）；从发育异常发展为早期癌的显著风险预测指标是p53（OR=6.63，p=0.0001）和Rb（OR=3.81，p=0.056）；而进一步进展的显著风险预测指标是EGFR（OR=5.50，p=0.0001）、Stat3（OR=4.49，p=0.0001）、H-ras（OR=4.05，p=0.001）和c-myc（OR=2.99，p=0.015）。细胞周期蛋白D1在连接上游信号通路与细胞周期调控方面起着关键作用。有丝分裂信号通路的基因产物在增生-发育异常-早期癌-晚期癌序列中与细胞周期调节蛋白发挥着同样重要的作用，共同可为定义癌前病变以及预测恶性转化和肿瘤进展风险提供一组参考标志物。
