Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers
Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers
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DOI：
10.1007/s10549-013-2763-z
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发表时间：
2014-01-01
影响因子：
3.8
通讯作者：
Pusztai, Lajos
中科院分区：
文献类型：
--
作者：
Itoh, Mitsuya;Iwamoto, Takayuki;Pusztai, Lajos
我们通过免疫组化（IHC）或荧光原位杂交检测孕激素受体（PR）阳性但ER和HER 2阴性的I-III期乳腺癌中雌激素受体（ER）mRNA表达和分子亚型。作为常规临床评估的一部分，通过IHC测定ER、PR和HER 2状态（N = 501）。基因表达谱分析采用AffyphineU 133 A基因芯片。我们比较了ER/PR阳性（n = 223）、ER阳性/PR阴性（n = 73）、ER阴性/PR阳性（n = 20）和三阴性（n = 185）癌症中ESR 1和MKI 67 mRNA的表达、PAM 50分类器的分子亚型分布、对内分泌治疗指数的敏感性和DLDA 30化疗反应预测标志。所有患者均接受蒽环类和紫杉烷类药物的新辅助化疗，仅在ER或PR > 10%阳性时进行辅助内分泌治疗。ESR 1在25%的ER阴性/PR阳性、79%的ER阳性/PR阴性、96%的ER/PR阳性和12%的三阴性癌症中表达高。ER阴性/PR阳性和三阴性队列中的平均MKI 67表达显著更高。在ER阴性/PR阳性患者中，15%为管腔A型，5%为管腔B型，65%为基底样。ER阴性/PR阳性患者的无复发生存率与ER阳性癌症相当，优于三阴性队列。只有20- 25%的ER阴性/PR阳性肿瘤显示出ER阳性癌症的分子特征。在这种罕见的患者亚组中，（i）第二次基于RNA的评估可能有助于识别少数ESR 1 mRNA阳性的管腔型癌症，（ii）最安全的临床方法可能是考虑辅助内分泌和化疗。
We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy.