组织微阵列与全切片及生化分析的比较。丹麦乳腺癌协作组82 b&c的亚组分析。
Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG 82 b&c.
作者信息
Kyndi M, Sørensen F B, Knudsen H, Overgaard M, Nielsen H M, Andersen J, Overgaard J
机构信息
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
出版信息
Acta Oncol. 2008;47(4):591-9. doi: 10.1080/02841860701851871.
INTRODUCTION
The tissue microarray (TMA) technique comprises the potential of significantly reducing time and tissue spent on slicing and performing immunohistochemical (IHC) stainings of paraffin-embedded tumor tissue. Tissue heterogeneity is an argument against using TMAs, which has been dealt with by increasing the size and number of cores punched from each tumor. No consensus exists on the most optimal size, number, and position of TMA cores in the donor paraffin block and no information exist regarding agreement between TMA cores from two different paraffin blocks from the same tumor or between TMA cores and biochemical analyses.
PATIENTS AND METHODS
A central and a peripheral 1mm core and a whole section from each of 54 paraffin blocks from 27 breast cancers included in a one-institution cohort, and a single 1mm central TMA core, from each breast tumor from 1000 patients included in the DBCG82 b&c trials, were IHC stained for ER, PgR and HER2. In addition, ER and PgR were measured in the DBCG82 b&c trials by a biochemical analysis. Statistical analyses included Kappa statistics, Kaplan-Meier survival curves, Log-rank tests, and Cox regression hazards analyses.
RESULTS AND CONCLUSION
IHC stainings for ER, PgR, and HER2 showed a substantial agreement between a single 1mm TMA core and the corresponding whole section, between central and peripheral cores, and between cores from two different paraffin blocks from the same tumor. In addition, a fine agreement was found for ER and PgR between IHC stainings of TMA cores and biochemical analyses. Divergence between IHC and biochemical analyses was predominantly due to the chosen thresholds. IHC staining of one 1mm core from each tumor revealed a significant independent prognostic value of PgR and HER2 on overall survival. In conclusion, IHC stainings for ER, PgR, and HER2 of just a single 1mm TMA core seems to be sufficient, as no significant heterogeneity was noticed.
引言
组织微阵列（TMA）技术具有显著减少对石蜡包埋肿瘤组织进行切片和免疫组织化学（IHC）染色所需时间和组织的潜力。组织异质性是反对使用TMA的一个理由，这一问题已通过增加从每个肿瘤中取出的芯块的大小和数量来解决。对于供体石蜡块中TMA芯块的最佳大小、数量和位置，目前尚无共识，并且关于来自同一肿瘤的两个不同石蜡块中的TMA芯块之间或TMA芯块与生化分析之间的一致性也没有相关信息。
患者与方法
对来自一家机构队列中27例乳腺癌的54个石蜡块中的每一个，取一个中央和一个外周1毫米芯块以及一个全切片，并且对来自DBCG82 b&c试验中1000例患者的每个乳腺肿瘤取一个单一的1毫米中央TMA芯块，进行雌激素受体（ER）、孕激素受体（PgR）和人表皮生长因子受体2（HER2）的免疫组化染色。此外，在DBCG82 b&c试验中通过生化分析测量ER和PgR。统计分析包括Kappa统计、Kaplan-Meier生存曲线、对数秩检验和Cox回归风险分析。
结果与结论
ER、PgR和HER2的免疫组化染色显示，单个1毫米TMA芯块与相应的全切片之间、中央芯块与外周芯块之间以及来自同一肿瘤的两个不同石蜡块中的芯块之间具有高度一致性。此外，在TMA芯块的免疫组化染色与生化分析之间，发现ER和PgR具有良好的一致性。免疫组化与生化分析之间的差异主要归因于所选择的阈值。对每个肿瘤的一个1毫米芯块进行免疫组化染色显示，PgR和HER2对总生存期具有显著的独立预后价值。总之，由于未发现显著的异质性，仅对单个1毫米TMA芯块进行ER、PgR和HER2的免疫组化染色似乎就足够了。
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