Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers.
Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers.
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基础样的表型与雌激素受体阴性乳腺癌中的患者存活无关。
DOI：
10.1186/bcr1649
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发表时间：
2007
影响因子：
7.4
通讯作者：
Isola, Jorma
中科院分区：
文献类型：
--
作者：
Jumppanen, Mervi;Gruvberger-Saal, Sofia;Kauraniemi, Paivikki;Tanner, Minna;Bendahl, Par-Ola;Lundin, Mikael;Krogh, Morten;Kataja, Pasi;Borg, Ake;Ferno, Marten;Isola, Jorma
基底表型或基底样乳腺癌的特征在于基底上皮细胞角蛋白（CK 5/14/17）表达、阴性雌激素受体（ER）状态和独特的基因表达特征。我们研究了免疫组化（IHC）和cDNA微阵列确定的基础表型肿瘤的临床和生物学特征，特别是在ER阴性亚组。IHC用于评估445例II期乳腺癌的CK 5/14状态。用cDNA微阵列研究了CK 5/14免疫阳性肿瘤的基因表达特征在一个子集（100）的乳腺肿瘤（包括50个ER阴性肿瘤）内。评估了通过CK 5/14 IHC和基因表达特征确定的基础表型肿瘤的存活率。在375份可分析的肿瘤标本中，48份（13%）为CK 5/14免疫化学阳性。我们发现CK 5/14阳性肿瘤患者在最初几年的无远处转移生存率（3年风险比（HR）2.23，95%置信区间（CI）1.17至4.24，p = 0.01; 5年HR 1.80，95% CI 1.02至3.15，p = 0.04），但在随访期结束时失去了显著性（10年HR 1.43，95% CI 0.84 - 2.43，p = 0.19）。ER阴性肿瘤组中经免疫组化确定的CK 5/14阳性肿瘤的基因表达谱涉及1，713个不同表达的基因（p < 0.05）。这些基因的前500个的分层聚类分析也在ER阴性肿瘤实体内形成一个基底样和一个非基底样簇。一个高度一致的分类，可以构建一个已公布的基因集（索利的内在基因集，一致性90%）。这两个基因组都鉴定出一个基底样簇，包括大多数CK 5/14阳性肿瘤，但也包括化学上CK 5/14阴性的肿瘤。在ER阴性肿瘤实体中，通过免疫组织化学或基于基因表达的分类确定的非基底和基底样肿瘤之间没有生存差异。基底细胞角蛋白阳性肿瘤具有与其他ER阴性肿瘤不同的生物学基因表达特征。即使基底细胞角蛋白表达预测非选择性肿瘤的早期复发，基底肿瘤的临床结局与非基底ER阴性肿瘤相似。免疫组化基底细胞角蛋白阳性肿瘤几乎总是属于基底样基因表达谱，但这一集群也包括一些基底细胞角蛋白阴性肿瘤。
Basal-phenotype or basal-like breast cancers are characterized by basal epithelium cytokeratin (CK5/14/17) expression, negative estrogen receptor (ER) status and distinct gene expression signature. We studied the clinical and biological features of the basal-phenotype tumors determined by immunohistochemistry (IHC) and cDNA microarrays especially within the ER-negative subgroup. IHC was used to evaluate the CK5/14 status of 445 stage II breast cancers. The gene expression signature of the CK5/14 immunopositive tumors was investigated within a subset (100) of the breast tumors (including 50 ER-negative tumors) with a cDNA microarray. Survival for basal-phenotype tumors as determined by CK5/14 IHC and gene expression signature was assessed. From the 375 analyzable tumor specimens, 48 (13%) were immunohistochemically positive for CK5/14. We found adverse distant disease-free survival for the CK5/14-positive tumors during the first years (3 years hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.17 to 4.24, p = 0.01; 5 years HR 1.80, 95% CI 1.02 to 3.15, p = 0.04) but the significance was lost at the end of the follow-up period (10 years HR 1.43, 95% CI 0.84 to 2.43, p = 0.19). Gene expression profiles of immunohistochemically determined CK5/14-positive tumors within the ER-negative tumor group implicated 1,713 differently expressed genes (p < 0.05). Hierarchical clustering analysis with the top 500 of these genes formed one basal-like and a non-basal-like cluster also within the ER-negative tumor entity. A highly concordant classification could be constructed with a published gene set (Sorlie's intrinsic gene set, concordance 90%). Both gene sets identified a basal-like cluster that included most of the CK5/14-positive tumors, but also immunohistochemically CK5/14-negative tumors. Within the ER-negative tumor entity there was no survival difference between the non-basal and basal-like tumors as identified by immunohistochemical or gene-expression-based classification. Basal cytokeratin-positive tumors have a biologically distinct gene expression signature from other ER-negative tumors. Even if basal cytokeratin expression predicts early relapse among non-selected tumors, the clinical outcome of basal tumors is similar to non-basal ER-negative tumors. Immunohistochemically basal cytokeratin-positive tumors almost always belong to the basal-like gene expression profile, but this cluster also includes few basal cytokeratin-negative tumors.
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影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
5
作者：
Korsching, E;Packeisen, J;Buerger, H
通讯作者：
Buerger, H
影响因子：
7.3
作者：
El-Rehim, DMA;Pinder, SE;Ellis, IO
通讯作者：
Ellis, IO
影响因子：
7.5
作者：
Livasy, CA;Karaca, G;Perou, CM
通讯作者：
Perou, CM
影响因子：
5.8
作者：
Bouton, CMLS;Pevsner, J
通讯作者：
Pevsner, J