The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment
The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment
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DOI：
10.1159/000292644
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发表时间：
2011-01-01
期刊：
影响因子：
5
通讯作者：
Zhuang, Zhengping
中科院分区：
文献类型：
--
作者：
Leong, Anthony S. -Y.;Zhuang, Zhengping
病理检查一直是癌症诊断的金标准，其作用还包括阐明病因、发病机制、临床病理相关性和预后。新技术的出现以及对乳腺癌异质性的认识已将焦点转移到预后上，人们越来越关注形态学特征和与预后相关的免疫组织化学标记物的识别。然而，尽管在乳腺癌免疫组织化学生物标志物的鉴定上投入了大量精力，但大多数标志物尚未被证明在多变量分析中具有价值，只有雌激素受体、孕激素受体和 Her2/neu 表达仍然是病理检查的重要组成部分。这 3 个标志物最初用于预测，但它们在治疗中的作用也使其具有预测价值。较新的分子方法，尤其是高通量技术表明，即使是形态相似的乳腺癌亚型也可能表现出分子异质性；此外，浸润性导管癌可分为至少 4 种分子亚型，分别为管腔型（ER+、PR+ 和 Her2/neu-）、Her2 过表达型（ER-、PR- 和 Her2/neu+）、基底样型（ER-、PR-、Her2/neu- 和 CK5/6+、EGFR+）和正常乳腺样型（ER-、PR- 和 Her2/neu-)，各自具有不同的临床结果。这些亚型中增殖基因表达的重要性已得到证明，替代免疫组织化学标记包括 ER、PR、Her2/neu 和 Ki67，用于更昂贵的分子测试。重要的是，分子技术不仅为乳腺癌的异质性提供了进一步的见解，而且还通过鉴定对肿瘤细胞增殖和存活至关重要的信号分子，开辟了新的治疗途径。因此，癌症的治疗从“一刀切”的传统方法转变为针对肿瘤具体特征的个性化治疗。病理学家继续在诊断中发挥其传统作用，但作为切除组织的提供者，病理学家现在还具有识别对治疗操作有反应的生物标志物的额外作用，从而作为诊断肿瘤学家在乳腺癌的治疗中发挥着不可分割的作用。版权所有 (C) 2011 S. Karger AG，巴塞尔
Pathological examination has been the gold standard for diagnosis in cancer and its role has also included the elucidation of etiology, pathogenesis, clinicopathological correlation, and prognostication. The advent of newer technologies and the realization that breast cancer is heterogeneous has shifted the focus to prognostication, with increased attention being paid to the identification of morphological features and immunohistochemical markers of prognostic relevance. However, despite the massive efforts invested in the identification of immunohistochemical biomarkers in breast cancer the majority have not proven to be of value in multivariate analyses and only estrogen receptor, progesterone receptor, and Her2/neu expression have remained essential components of pathological examination. These 3 markers were initially employed for prognostication but their role in treatment also rendered them of predictive value. Newer molecular methods, especially high-throughput technologies, have shown that even morphologically similar subtypes of breast cancer can show molecular heterogeneity; moreover, infiltrating ductal carcinoma can be separated into at least 4 molecular subtypes designated luminal (ER+, PR+, and Her2/neu-), Her2 overexpressing (ER-, PR-, and Her2/neu+), basal-like (ER-, PR-, Her2/neu-, and CK5/6+, EGFR+), and normal breast-like (ER-, PR-, and Her2/neu-), each with different clinical outcomes. The importance of proliferative gene expression in these subtypes has been demonstrated and surrogate immunohistochemical markers include ER, PR, Her2/neu, and Ki67 for the more expensive molecular tests. Molecular technologies, importantly, have not only provided further insights into the heterogeneity of breast cancer but have also opened new avenues for treatment through the identification of signaling molecules important in the proliferation and survival of the neoplastic cells. The treatment of cancer thus shifts from the conventional approach of 'one size fits all' to one of personalized treatment tailored to the specific characteristics of the tumor. Pathologists continue to play their traditional role in diagnosis but, as purveyors of the excised tissue, pathologists now have the additional role of identifying biomarkers responsive to therapeutic manipulation, thus playing an inextricable role as diagnostic oncologists in the management of breast cancer. Copyright (C) 2011 S. Karger AG, Basel