Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry.
Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry.
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DOI：
10.18632/oncotarget.18006
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Wallwiener M
中科院分区：
文献类型：
--
作者：
Stefanovic S;Wirtz R;Deutsch TM;Hartkopf A;Sinn P;Varga Z;Sobottka B;Sotiris L;Taran FA;Domschke C;Hennigs A;Brucker SY;Sohn C;Schuetz F;Schneeweiss A;Wallwiener M
原发性（PT）和转移性肿瘤（MT）部位之间的生物标志物变化可能在个体化治疗策略中具有重要意义，并且可能由实际克隆进化、生物标志物转换或诊断测试的技术限制引起。本研究通过mRNA定量探索了67例不同肿瘤亚型和转移部位的乳腺癌（BC）进展期间的生物标志物转换，随后分析了实时qPCR和免疫组织化学（IHC）之间的一致性。在福尔马林固定、石蜡包埋的PT和MT组织切片上进行雌激素受体（ER）、孕激素受体（PR）、HER 2和Ki-67的免疫染色。使用ESR 1、PCR、ERBB 2和MKI 67以及参考基因B2 M和CALM 2的多重RT-qPCR试剂盒进行RT-qPCR。随后测量肿瘤生物标志物mRNA表达以检测转化，结果显示，与PT相比，所有肿瘤亚型的MT中ESR 1和PGR mRNA以及MKI 67上调均显着降低（均p < 0.001），而三阴性PT患者的MT中ERBB 2上调（p = 0.023）。此外，ERBB 2 mRNA在MT脑活检中上调，特别是来自三阴性PT的那些（p = 0.023）。对于ER/ESR 1（PT中为81%（κ 0.51），MT中为84%（κ 0.34））、PR/PGR（PT中为70%（κ 0.10），MT中为78%（κ −0.32））和HER 2/ERBB 2（PT中为100%，MT中为89%），观察到RT-qPCR和IHC之间的高度一致性。由于受体转换导致的PT和MT的mRNA生物标志物评估之间的不一致性要求对BC肿瘤生物标志物进行动态监测。总体而言，在原发性和转移性肿瘤中，BC靶基因及其mRNA表达的RT-qPCR评估与IHC蛋白分析高度一致。
Biomarker changes between primary (PT) and metastatic tumor (MT) site may be significant in individualizing treatment strategies and can result from actual clonal evolution, biomarker conversion, or technical limitations of diagnostic tests. This study explored biomarker conversion during breast cancer (BC) progression in 67 patients with different tumor subtypes and metastatic sites via mRNA quantification and subsequently analyzed the concordance between real-time qPCR and immunohistochemistry (IHC). Immunostaining for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 was performed on formalin-fixed, paraffin-embedded PT and MT tissue sections. RT-qPCR was performed using a multiplex RT-qPCR kit for ESR1, PGR, ERBB2, and MKI67 and the reference genes B2M and CALM2. Subsequent measurement of tumor biomarker mRNA expression to detect conversion revealed significant decreases in ESR1 and PGR mRNA and MKI67 upregulation (all p < 0.001) in MT compared to PT of all tumor subtypes and ERBB2 upregulation in MT from triple-negative PT patients (p = 0.023). Furthermore, ERBB2 mRNA was upregulated in MT brain biopsies, particularly those from triple-negative PTs (p = 0.023). High concordance between RT-qPCR and IHC was observed for ER/ESR1 (81%(κ 0.51) in PT and 84%(κ 0.34) in MT, PR/PGR (70%(κ 0.10) in PT and 78% (κ −0.32) in MT), and for HER2/ERBB2 (100% in PT and 89% in MT). Discordance between mRNA biomarker assessments of PT and MT resulting from receptor conversion calls for dynamic monitoring of BC tumor biomarkers. Overall, RT-qPCR assessment of BC target genes and their mRNA expression is highly concordant with IHC protein analysis in both primary and metastatic tumor.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
11.5
作者：
Hayes, Daniel F.;Cristofanilli, Massimo;Terstappen, Leon W. W. M.
通讯作者：
Terstappen, Leon W. W. M.
DOI：
10.1186/bcr2645
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hoefnagel LD;van de Vijver MJ;van Slooten HJ;Wesseling P;Wesseling J;Westenend PJ;Bart J;Seldenrijk CA;Nagtegaal ID;Oudejans J;van der Valk P;van der Groep P;de Vries EG;van der Wall E;van Diest PJ
通讯作者：
van Diest PJ
DOI：
10.1186/bcr2907
发表时间：
2011-06-15
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Giuliano M;Giordano A;Jackson S;Hess KR;De Giorgi U;Mego M;Handy BC;Ueno NT;Alvarez RH;De Laurentiis M;De Placido S;Valero V;Hortobagyi GN;Reuben JM;Cristofanilli M
通讯作者：
Cristofanilli M
影响因子：
45.3
作者：
Gutierrez, MC;Detre, S;Dowsett, M
通讯作者：
Dowsett, M