Viale Giuseppe, Slaets Leen, de Snoo Femke A, Bogaerts Jan, Russo Leila, van't Veer Laura, Rutgers Emiel J T, Piccart-Gebhart Martine J, Stork-Sloots Lisette, Dell'Orto Patrizia, Glas Annuska M, Cardoso Fatima
Department of Pathology, European Institute of Oncology and University of Milan, Via Ripamonti 435, 20141, Milan, Italy.
Department of Statistics, European Organization for Research and Treatment of Cancer, Brussels, Belgium.
Breast Cancer Res Treat. 2016 Feb;155(3):463-9. doi: 10.1007/s10549-016-3690-6. Epub 2016 Jan 28.
Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.
准确识别最有可能从辅助性全身治疗中获益的乳腺癌患者至关重要。更好地理解不同方法之间的差异有助于改进雌激素受体（ER）、孕激素受体（PgR）和人表皮生长因子受体2（HER-2）的评估。这项预先计划的转化研究旨在调查MINDACT试验中ER、PgR和HER-2状态的中心免疫组化（IHC）/荧光原位杂交（FISH）评估与基因芯片mRNA读数之间的相关性，并确定是否有任何不一致可归因于肿瘤内异质性或标本中的导管原位癌（DCIS）和正常组织成分。MINDACT是一项国际前瞻性随机III期试验，旨在研究MammaPrint在选择早期乳腺癌患者进行辅助化疗（n = 6694例患者）中的临床效用。基因表达数据通过TargetPrint获得；IHC和/或FISH由中心进行评估（n = 5788；86%）。对中心提交的福尔马林固定石蜡包埋（FFPE）组织块进行宏观和微观评估，确定了1427例将同一样本提交进行基因表达分析的病例。TargetPrint ER与中心病理学的阳性一致性为98%，阴性一致性为95%。PgR的相应数字分别为85%和94%，HER-2为72%和99%。当分析肿瘤组织的相同或不同部分，或在进行mRNA检测的样本中包括DCIS和/或正常组织时，mRNA与中心蛋白的一致性没有差异。这是首次对乳腺癌标志物蛋白质和mRNA分析之间的不一致率进行大规模分析，并研究肿瘤内异质性、DCIS或正常组织成分作为不一致潜在原因的情况。观察到的PgR和HER-2在mRNA和蛋白质评估之间的差异需要进一步研究；目前的分析不支持肿瘤内异质性或DCIS和正常组织成分是不一致的可能原因。
