Breast cancer is a heterogeneous disease comprising the estrogen receptor (ER)-positive luminal subtype which is subdivided into luminal A and luminal B and ER-negative breast cancer which includes the triple-negative subtype. This study has four aims: 1) to examine whether Minichromosome Maintenance (MCM)2, MCM4, and MCM6 can be used as markers to differentiate between luminal A and luminal B subtypes; 2) to study whether MCM2, MCM4, and MCM6 are highly expressed in triple-negative breast cancer, as there is an urgent need to search for surrogate markers in this aggressive subtype, for drug development purposes; 3) to compare the prognostic values of these markers in predicting relapse-free survival; and 4) to compare the three approaches used for scoring the protein expression of these markers by immunohistochemistry (IHC). MCM2, MCM4, MCM6, and MKI67 mRNA expression was first studied using in silico analysis of available breast cancer datasets. We next used IHC to evaluate their protein expression on tissue microarrays using three scoring methods. MCM2, MCM4, and MCM6 can help in distinction between luminal A and luminal B whose therapeutic management and clinical outcomes are different. MCM2, MCM4, MCM6, and Ki-67 are highly expressed in breast cancer of high histological grades that comprise clinically aggressive tumors such as luminal B, HER2-positive, and triple-negative subtypes. Low transcript expression of these markers is associated with increased probability of relapse-free survival. A positive relationship exists among the three scoring methods of each of the four markers. An independent validation cohort is needed to confirm their clinical utility.

中文翻译：

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乳腺癌中的MCM2，MCM4和MCM6：在诊断和预后方面的临床应用。

乳腺癌是异质性疾病，包括雌激素受体（ER）阳性管腔亚型，细分为管腔A和管腔B，而ER阴性乳腺癌则包括三阴性。这项研究有四个目标：1）检查微染色体维持（MCM）2，MCM4和MCM6是否可以用作区分腔A和腔B亚型的标志物；2）研究MCM2，MCM4和MCM6在三阴性乳腺癌中是否高表达，因为迫切需要在这种侵袭性亚型中寻找替代标记，以用于药物开发；3）比较这些标志物在预测无复发生存中的预后价值；和4）比较通过免疫组织化学（IHC）评分这些标记蛋白表达的三种方法。MCM2，MCM4，MCM6，首先使用现有乳腺癌数据集的计算机分析来研究MKI67和mRNA的表达。接下来，我们使用IHC使用三种评分方法评估其在组织微阵列上的蛋白质表达。MCM2，MCM4和MCM6可以帮助区分治疗管理和临床结果不同的腔A和腔B。MCM2，MCM4，MCM6和Ki-67在高组织学等级的乳腺癌中高表达，这些乳腺癌包括临床上侵袭性肿瘤，例如腔B型，HER2阳性和三阴性亚型。这些标志物的低转录表达与无复发生存的可能性增加有关。四个标记中每个标记的三种评分方法之间存在正相关关系。需要一个独立的验证队列来确认其临床实用性。