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首页> 外文期刊>American Journal of Translational Research >Evaluation of CCND1 amplification and CyclinD1 expression: diffuse and strong staining of CyclinD1 could have same predictive roles as CCND1 amplification in ER positive breast cancers
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Evaluation of CCND1 amplification and CyclinD1 expression: diffuse and strong staining of CyclinD1 could have same predictive roles as CCND1 amplification in ER positive breast cancers

机译：CCND1扩增和CyclinD1表达的评估：ER阳性乳腺癌中CyclinD1的弥漫性和强染色可能具有与CCND1扩增相同的预测作用

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CCND1 is amplified in around 10-20% of primary breast cancers and preferentially occurs in ER positive tumors. Though CCND1 amplification was reported predicting poor response of adjuvant tamoxifen treatment and poor prognosis in ER positive breast cancers, there were controversial data regarding the predicting value of CyclinD1 protein overexpression. In this study, we detected CyclinD1 expression using immunohistochemistry and CCND1 gene copy number using fluorescence in situ hybridization (FISH) in 355 invasive breast cancers with foci ductal carcinoma in situ (DCIS). CCND1 amplification was founded in 52 (14.6%) cases all of which showed moderate to strong CyclinD1 expression. However, majority of CCND1- tumors exhibited mild to moderate CyclinD1 staining. There were identical alterations in DCIS and the invasive lesions within the same tumor. CCND1 amplification was positively correlated with ER, PR and lymph node status (P<0.001) while negatively correlated with HER-2 amplification and p53 status (P<0.05). The majority of the CCND1 amplification/high CyclinD1 breast cancers were luminal B type while basal-like type often lost the expression of this protein. The ROC curve analysis showed that a cut-off point at which the immunostaining score of CyclinD1 is 6.5 could predict CCND1 gene amplification in breast cancer. This study indicated loss expression of CyclinD1 might be an important event in the tumorigenesis in basal-like breast cancers. Further, we confirmed an optimal cut-off point of immunostaining scores of CyclinD1 protein which could be used to predict the status of CCND1 gene and identify a subgroup of ER positive breast cancers with poor response to endocrine agents.
机译：CCND1在大约10-20％的原发性乳腺癌中被扩增，并优先出现在ER阳性肿瘤中。虽然据报道CCND1扩增预测了他莫昔芬辅助治疗的不良反应以及ER阳性乳腺癌的预后不良，但关于CyclinD1蛋白过表达的预测价值仍有争议数据。在这项研究中，我们检测了355例原发灶性导管癌（DCIS）的浸润性乳腺癌中，使用免疫组织化学检测了CyclinD1的表达，并使用荧光原位杂交（FISH）检测了CCND1基因的拷贝数。 CCND1扩增建立在52（14.6％）例中，所有病例均显示中等至强CyclinD1表达。但是，大多数CCND1肿瘤表现出轻度至中度CyclinD1染色。 DCIS和同一肿瘤内的浸润性病变有相同的改变。 CCND1扩增与ER，PR和淋巴结状态呈正相关（P <0.001），而与HER-2扩增和p53状态呈负相关（P <0.05）。大多数CCND1扩增/高CyclinD1乳腺癌是管腔B型，而基底样型则常常失去该蛋白的表达。 ROC曲线分析表明，CyclinD1的免疫染色评分为6.5的临界点可以预测CCND1基因在乳腺癌中的扩增。这项研究表明CyclinD1的丧失表达可能是基底样乳腺癌的肿瘤发生中的重要事件。此外，我们确定了CyclinD1蛋白免疫染色评分的最佳临界点，可用于预测CCND1基因的状态并鉴定对内分泌药物反应不良的ER阳性乳腺癌亚组。

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