J Natl Cancer Inst：两项标志物可预测早期乳腺癌预后
2013-01-10 J Natl Cancer Inst dxy echo1166
有一部分早期乳腺癌(DCIS)患者会进展成侵袭性乳腺癌。然而，目前还没有标志物能将这部分高危女性患者从低危患者中区别开来。为了探究这样的标记物是否存在，来自德克萨斯大学西南医学中心的Erik S. Knudsen等进行了相关研究，其结果发表在JNCI 12月的在线期刊上。 研究者主要对两个主要的抑癌基因——视网膜胚胎母细胞瘤(RB)和同源性磷
有一部分早期乳腺癌(DCIS)患者会进展成侵袭性乳腺癌。然而，目前还没有标志物能将这部分高危女性患者从低危患者中区别开来。为了探究这样的标记物是否存在，来自德克萨斯大学西南医学中心的Erik S. Knudsen等进行了相关研究，其结果发表在JNCI 12月的在线期刊上。
研究者主要对两个主要的抑癌基因——视网膜胚胎母细胞瘤(RB)和同源性磷酸酶-张力蛋白 (PTEN)进行了评估，对这两个抑癌基因和任何单侧乳腺癌发病或进展为侵袭性乳腺癌风险之间的联系。研究者纳入了236名接受保乳手术的DCIS患者数据，这些患者接受长期随访，采用免疫组化方法评估RB和PTEN表达情况。在MCF10A细胞中评估RB和/或PTEN缺失的效果。采用单变量分析和多变量Cox回归模型计算HR。所有的统计检验皆为双侧。
在DCIS患者中，RB免疫反应性缺失与IBE发生和IBC复发风险增高显著相关，HR分别为2.64和4.66。在多变量分析中RB缺失具有极强的预测价值。PTEN缺失常见于DCIS的患者中，但是其与患者疾病的复发或进展不存在显著联系。然而，如果DCIS患者的RB和PTEN都缺失的话，会进一步增高其IBEs发生和IBC复发的风险，HR分别为3.39和6.1。MCF10A证实RB和PTEN缺失会影响增殖、运动和肿瘤的侵袭。
这些研究提示RB和PTEN结合能预测患者的预后，能给患者带来治疗获益。
Background A subset of patients with ductal carcinoma in situ (DCIS) will progress to invasive breast cancer. However, there are currently no markers to differentiate women at high risk from those at lower risk of developing invasive disease.
Methods The association of two major tumor suppressor genes, retinoblastoma (RB) and phosphatase and tensin homolog (PTEN), with risk of any ipsilateral breast event (IBE) or progression to invasive breast cancer (IBC) was analyzed using data from 236 DCIS patients treated with breast conserving surgery with long-term follow-up. RB and PTEN expression was assessed with immunohistochemistry. The functional effects of RB and/or PTEN loss were modeled in MCF10A cells. Hazard ratios (HRs) were estimated with univariate and multivariable Cox regression models. All statistical tests were two-sided.
Results Loss of RB immunoreactivity in DCIS was strongly associated with risk of IBE occurrence (HR = 2.64; 95% confidence interval [CI] = 1.64 to 4.25) and IBC recurrence (HR = 4.66; 95% CI = 2.19 to 9.93). The prognostic power of RB loss remained statistically significant in multivariable analyses. PTEN loss occurred frequently in DCIS but was not associated with recurrence or progression. However, patients with DCIS lesions that were both RB and PTEN deficient were at further increased risk for IBEs (HR = 3.39; 95% CI = 1.92 to 5.99) and IBC recurrence (HR = 6.1, 95% CI = 2.5 to 14.76). Preclinical modeling in MCF10A cells demonstrated that loss of RB and PTEN impacted proliferation, motility, and invasive properties.
Conclusions These studies indicate that RB and PTEN together have prognostic utility and could be used to target aggressive treatment for patients with the greatest probability of benefit.
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