Poor prognostic significance of unamplified chromosome 17 polysomy in invasive breast carcinoma
Poor prognostic significance of unamplified chromosome 17 polysomy in invasive breast carcinoma
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DOI：
10.1038/modpathol.2009.61
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发表时间：
2009-08-01
期刊：
影响因子：
7.5
通讯作者：
Silverman, Jan F.
中科院分区：
文献类型：
--
作者：
Krishnamurti, Uma;Hammers, Jennifer L.;Silverman, Jan F.
人表皮生长因子受体2（HER 2）癌蛋白在约20%的乳腺癌中过表达，其中HER 2基因扩增导致绝大多数患者的蛋白质过表达。乳腺癌的一个子集具有染色体17异染色体，这是由于17单体性（17号染色体的单拷贝）或多体性（17号染色体的拷贝数增加）。虽然HER 2过表达是乳腺癌的一个既定的不良预后因素，未扩增的17号染色体多体性的作用是不确定的，有一个关于17号染色体异体性与浸润性乳腺癌的重要预后和预测病理因素的相关性的文献很少。此外，虽然显示HER 2扩增伴或不伴17号多体性的患者接受曲妥珠单抗治疗伴或不伴其他化疗，但未扩增的17号染色体多体性患者的治疗尚未明确。目前，这些患者中的大多数接受的治疗与既没有扩增也没有17多体性的患者类似。本研究的目的是比较浸润性乳腺癌患者的一些预后和预测因素与未扩增的17号染色体多体性与HER 2基因扩增的情况下，既没有扩增或多体性。我们发现，浸润性乳腺癌与未扩增的17号染色体多体性与几个不良预后指标，如较高的核分级，有丝分裂活性，诺丁汉评分，组织学分级，肿瘤分期，和更大的雌激素受体阴性倾向于扩增组，与既没有扩增或多体性的患者相比。尽管大多数未扩增17多体性患者的免疫组化评分为2+模棱两可，但少数患者的阳性评分为3+。在一些患者中，未扩增的多体性沿着3+蛋白表达的不良作用增加，支持这些患者应考虑接受曲妥珠单抗和/或蒽环类药物治疗的观点。Modern Pathology（2009）22，1044-1048; doi：10.1038/modpathol. 2009.61; 2009年4月24日在线发布
The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of chromosome 17) or polysomy (increased copy numbers of chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified chromosome 17 polysomy is uncertain and there is a paucity of literature on the correlation of chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified chromosome 17 polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified chromosome 17 polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or polysomy. We found that invasive breast carcinomas with unamplified chromosome 17 polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or polysomy. Although most patients with unamplified 17 polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines. Modern Pathology (2009) 22, 1044-1048; doi: 10.1038/modpathol. 2009.61; published online 24 April 2009