Prognostic Significance of Progesterone Receptor-Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer
Prognostic Significance of Progesterone Receptor-Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer
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DOI：
10.1200/jco.2012.43.4134
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发表时间：
2013-01-10
影响因子：
45.3
通讯作者：
Perou, Charles M.
中科院分区：
文献类型：
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作者：
Prat, Aleix;Cheang, Maggie Chon U.;Perou, Charles M.
目的目前基于免疫组化（IHC）的管腔A和B乳腺癌的定义与基于多基因表达的检测相比是不完善的。在这项研究中，我们试图通过检查基因组学定义的管腔A和B亚型的病理和基因表达特征来改善IHC亚型。不列颠哥伦比亚省癌症机构（BCCA）仅接受他莫昔芬治疗，Grupo Espanol de Investigacion en Cancer de Mama 9906试验，BCCA无全身治疗队列，PAM 50微阵列训练数据集和组合的公开可用的微阵列数据集。孕激素受体（PR）阳性肿瘤细胞的百分比预测生存的最佳截止值推导和独立测试。多变量考克斯模型被用来测试的预后significant. ResultsClinical管腔A和B亚型之间的比较一致确定较高的PR阳性率，人表皮生长因子受体2（HER 2）阴性，和组织学1级管腔A肿瘤。定量PR基因和蛋白表达也被发现是显着较高的管腔A肿瘤。在统计学上选择超过20%的PR阳性肿瘤细胞的经验性截止值，并证明其对于预测IHC定义的管腔A型肿瘤内的生存差异具有显著意义，与内分泌治疗给药无关。最后，没有额外的预后价值内激素受体（HR）阳性/HER 2阴性疾病的观察与使用的IHC 4评分时，使用内在的IHC为基础的亚型，包括超过20%的PR阳性肿瘤cells，反之亦然。ConclusionSemiquantitative IHC PR表达增加了预后价值内目前的IHC为基础的管腔A定义，提高了良好的结果乳腺癌的识别。新提出的基于IHC的管腔A型肿瘤的定义是HR阳性/HER 2阴性/Ki-67小于14%，PR大于20%。临床肿瘤学杂志31：203-209。(C)2012年美国临床肿瘤学会
PurposeCurrent immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes.Patients and MethodsGene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Espanol de Investigacion en Cancer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance.ResultsClinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa.ConclusionSemiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%. J Clin Oncol 31:203-209. (C) 2012 by American Society of Clinical Oncology