Molecular risk assessment for breast cancer development in patients with ductal hyperplasias
Molecular risk assessment for breast cancer development in patients with ductal hyperplasias
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DOI：
10.1158/1078-0432.ccr-07-4053
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发表时间：
2008-02-15
影响因子：
11.5
通讯作者：
DeWitty, Robert L.
中科院分区：
文献类型：
--
作者：
Poola, Indira;Abraham, Jessy;DeWitty, Robert L.
目的：据报道，美国每年约有 100 万女性被诊断患有良性乳腺病变，其中包括导管增生。最近对患有良性病变的女性进行的研究表明，其中约 8% 至 9% 的女性随后会发展为浸润性乳腺癌 (IBC)。然而，目前还没有办法识别患有导管增生且随后会患上癌症的女性中“真正的癌前组织”的亚类。本研究的目的是调查增生组织中已知的肿瘤启动子透明质酸氨基葡萄糖苷酶 1 (HYAL1) 的表达是否可识别“真正的癌前阶段”并预测随后的 IBC 发展。 实验设计：对各种组织学类型的存档良性组织和有关 IBC 发展/不发展的临床信息进行回顾性研究。对照组是来自没有 IBC 病史且诊断后 5 至 7 年内未发展为癌症的女性的增生组织 (n = 81)。测试组是来自癌症患者的增生组织（n = 82）。采用免疫组织化学方法研究HYAL1表达，并对结果进行统计分析与发生癌症的显着关联（P值）、特异性、敏感性、阳性预测值和阴性预测值。结果：HYAL1表达数据的统计分析显示其表达与随后的癌症发展之间存在非常高度显着的关联（P = 0）并且具有非常高的敏感性（0.83）、特异性（0.84）、阳性预测值（0.84）和阴性预测值(0.83).结论：导管增生组织中HYAL1的表达是IBC后续发展的有力预测因子；因此，它可以单独或与其他标记物结合用作诊断标记物来筛选良性组织以预测 IBC 的后续发展。癌前阶段的检测和治疗可以大大降低乳腺癌的发病率和死亡率。
Purpose: It has been reported that approximately a million women are diagnosed with benign breast lesions that include ductal hyperplasias per year in the United States. Recent studies that followed women with benign lesions have established that about 8% to 9% of them will subsequently develop invasive breast cancer (IBC). However, currently, there are no means of identifying a subclass of "true precancerous tissues" in women with ductal hyperplasias who will subsequently develop cancer. The purpose of this study is to investigate whether expression of hyaluronoglucosaminidase 1 (HYAL1), a known tumor promoter, in hyperplastic tissues identifies a "true precancerous stage" and predicts subsequent IBC development.Experimental Design: A retrospective study was conducted with archival benign tissues of various histologic types and clinical information on development/nondevelopment of IBC. The control group was hyperplastic tissues from women who had no prior history of IBC and did not develop cancer in 5 to 7 years after diagnosis (n = 81). The test group was hyperplastic tissues from patients who developed cancer (n = 82). HYAL1 expression was studied by immunohistochemistry, and the results were statistically analyzed for significant association to develop cancer (P value), specificity, sensitivity, positive predictive value, and negative predictive value.Results: Statistical analysis of HYAL1 expression data showed very highly significant association between its expression and subsequent cancer development (P = 0) and very high sensitivity (0.83), specificity (0.84), positive predictive value (0.84), and negative predictive value (0.83).Conclusions: The expression of HYAL1 in ductal hyperplastic tissues is a strong predictor of subsequent development of IBC; therefore, it can be applied as a diagnostic marker either singly or in combination with other marker(s) to screen benign tissues to predict subsequent development of IBC. Detection at the precancerous stage and treatment could drastically cut down breast cancer incidence and deaths from it.